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UC-NRLF 


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5ITY   OF    CHICAGO 

fOCHDEI)   BY  JOBS  D.  ROCKEPt.. 


THE  DECENNIAL  PUBLICATIONS 


THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNER 


HUBERT  RUSSELL  BENSLEY 


THE  DECENNIAL  PUBLICATIONS 


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THE    UNIVERSITY   OF    CHICAGO 

FOUNDED    BT  JOHN   D.  ROCKEFELLER 


THE  DECENNIAL  PUBLICATIONS 


THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNER 

BY 

ROBERT  RUSSELL  BENSLEY 


ASSISTANT  PROFES8OB  OF  ANATOMY 


PRINTED  FROM  VOLUME  X 


CHICAGO 

THE  UNIVERSITY  OF  CHICAGO  PRESS 
1903 


etouOGt 


Copyright  1903 
BY  THE  UNIVERSITY  OF  CHICAGO 


PRINTED  JUNE  1.  190S 


I—1  < 


THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNER 

ROBERT  RUSSELL  BENSLET      .    . 


I.     INTRODUCTION 

THE  appearance  recently  of  the  papers  of  Castellant-  (I'SSS)  :arid;Hbck;  i(ift99), 
dealing  with  the  structure  of  the  glands  of  Brunner,  is  a  sign  of  renewed  interest  in  a 
group  of  glands  which  has  baffled  both  the  physiologist  and  the  anatomist.  The 
efforts  of  the  former  have  been  largely  directed  toward  investigating  the  presence  or 
absence  of  digestive  ferments  in  the  succus  entericus  or  in  artificial  extracts  of  the 
gland.  Their  investigations,  undertaken  with  this  object  in  view,  have  not  yielded 
uniform  results,  although  the  recent  studies  of  Glassner  (1902)  confirm  the  observa- 
tions of  Grutzner  (1872)  that  the  glands  of  Brunner  contain  a  proteolytic  ferment. 

Wepfer  (1679),  who  discovered  the  glands  in  1679,  described  their  arrangement 
in  the  duodenum,  and  observed  that  when  macerated  in  water  they  liberated  an 
abundant  amount  of  mucus.  Eight  years  later  the  glands  were  described  more  fully 
by  Brunner,  who  regarded  them  as  a  sort  of  secondary  pancreas.  The  incorrectness 
of  this  view  was  shown  by  Claude  Bernard  (1856)  and  Middeldorpf  (1846),  both  of 
whom  pointed  out  that  the  secretion  of  the  glands  of  Brunner  differed  from  that  of 
the  pancreas. 

Budge  and  Krolow  (1870)  found  that  the  extract  of  the  glands  of  Brunner  would 
transform  starch  into  sugar,  would  dissolve  fibrin  in  acid  solution,  but  would  not  act 
on  coagulated  albumen  nor  on  fats. 

Grutzner  (1872),  following  up  his  observations  on  the  proteolytic  ferments  of  the 
pyloric  glands,  which  he,  in  common  with  Heidenhain  (1870)  and  Ebstein  (1870), 
regarded  as  pepsin-forming  glands  composed  of  chief  cells  like  those  of  the  fundus 
glands,  found  that  he  could  obtain  by  extraction  of  the  glands  of  Brunner  with  0.1  per 
cent,  hydrochloric  acid  a  solution  which  would  rapidly  digest  fibrin  in  acid  solutions. 

Similar  positive  results  as  to  the  existence  of  a  proteolytic  ferment  were  obtained 
by  Gachet  and  Pachon  (1898),  who  introduced  cylinders  of  coagulated  albumen  into 
the  isolated  duodenum  after  tying  the  pancreatic  duct. 

Recently  Glassner  (1902)  has  extended  to  the  study  of  the  ferments  of  the  glands 
of  Brunner  the  methods  which  he  had  already  employed  with  success  to  separate  the 
various  ferments  of  the  gastric  mucous  membrane.  The  extracts  which  he  obtained, 
after  taking  all  possible  precautions  to  exclude  the  glands  of  Lieberktihn  from  the 
material  extracted,  and  to  destroy  adherent  pepsin  and  trypsin,  were  inactive  with 
respect  to  starch,  cane  sugar,  and  fats.  On  the  other  hand,  they  digested  fibrin, 
serum  albumen,  and  coagulated  egg  albumen  in  solutions  containing  0.2-0.3  per  cent, 
of  hydrochloric  acid.  Moreover,  some  proteolytic  activity  was  still  displayed  when 

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THE  STKUCTUBE  OF  THE  GLANDS  OF  BRUNNEB 


the  solutions  were  rendered  neutral  or  slightly  alkaline.  The  specific  ferment  upon 
which  this  proteolytic  action  depended,  he  identified  with  the  pseudopepsin  which  he 
had  previously  extracted  from  the  pyloric  mucous  membrane.  It  differed  from  pepsin 
in  that  it  was  not  destroyed,  nor  its  activity  removed,  by  weak  solutions  of  sodium 
carbonate,  and  that  its  action  quickly  led  to  the  formation  of  tryptophan.  From 
trypsiii  at  Was  Jjstinfftiished  by  its  activity  in  acid  solutions. 

In  view.of  faepe  experiments  of  Glassner,  Grutzner,  and  others,  it  seems  certain 
that'VtIia.'aaJii'of  tiie.  glands -of  Brunner  contain  a  proteolytic  enzyme.  As  yet,  how- 
ever, it  is  not  known  whether  this  is  a  tissue  enzyme  concerned  in  some  of  the  various 
metabolic  processes  of  the  cell  itself  or  a  secreted  product  of  the  cell  designed  to  assist 
in  the  intestine,  in  the  transformation  of  the  proteids  of  the  food. 

Anatomically  the  main  points  of  interest,  as  far  as  the  glands  of  Brunner  are  con- 
cerned, have  been  the  form  and  distribution  of  the  glands,  the  question  as  to  whether 
they  are  mucous  or  serous  glands,  the  changes  they  exhibit  in  different  stages  of 
physiological  activity,  their  relationship  to  the  pyloric  glands,  and  their  phylogeny. 

The  question  of  the  form  of  the  glands  has  been  adequately  treated  by  Schwalbe 
(1872),  whose  conclusions  that  the  glands  of  Brunner  are  composed  of  ramifying 
tubules  into  which  acini  open  have  been  confirmed  with  some  additional  details,  by 
the  studies  of  Maziarski  (1902)  and  Peiser  (1903),  who  employed  the  reconstruction 
method  of  Born. 

Concerning  the  mucous  or  serous  nature  of  the  glands,  however,  there  is  not  the 
same  unanimity  of  opinion.  By  many  authors,  including  Schwalbe  (1872),  Heiden- 
hain  (1872),  Bentkowski  (1876),  and  Piersol  (1894),  they  have  been  compared  with 
the  pyloric  glands  which  these  authors  regarded  as  similar  to  the  chief  cells  of  the 
fundus  glands.  Claude  Bernard  (1856),  Sappey  (1876),  Renaut  (1879),  and  Berdal 
(1894)  regarded  them  as  mucous  glands.  Renaut  (1879),  basing  his  conclusions  on 
the  study  of  the  glands  of  Brunner  of  man,  regarded  them  as  structures  differentiated 
for  the  secretion  of  a  peculiar  mucus.  He  compared  them  with  the  pure  mucous 
glands  of  the  oesophagus  and  bronchi,  which,  according  to  him,  have  the  same  funda- 
mental structure  as  the  glands  of  Brunner. 

The  same  view,  in  a  somewhat  modified  form,  was  taken  by  Kuczynski  (1890), 
who  studied  in  a  number  of  representative  mammals  the  staining  reactions  of  the 
glandular  cells  by  means  of  certain  synthetic  dyes,  in  particular  victoria  blue,  azoblue, 
aniline  blue,  and  thionine.  These  he  found  to  stain  the  cells  of  the  glands  of 
Brunner  of  different  mammals  with  different  degrees  of  facility.  Some  cells,  for 
example  those  of  the  pig,  were  refractory  to  all  attempts  to  stain  them.  He  concluded 
that  in  the  latter  animal  the  cells  contained  no  mucin ;  that  in  others,  for  example  the 
rabbit  and  horse,  where  the  staining  was  feeble,  the  amount  of  mucin  was  small ;  and 
again  that  in  the  guinea  pig  and  ox,  where  the  cells  stained  strongly,  they  contained  a 
large  amount  of  mucin. 

Schaffer  (1891)  obtained  a  slight  violet  coloration  of  the  cells  of  the  glands  of 

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KOBEET  RUSSELL  BENSLEY 


Brunner  of  man  with  hsematoxylin ;  and  concluded  that  the  mucus  which  they  secreted 
differed  materially  from  that  formed  by  goblet  cells  and  by  the  salivary  glands. 

Castellant  (1898)  concluded  that  the  glands  of  Brunner  could  not  be  regarded  as 
mucous  glands,  but  should  rather  be  compared  with  the  pyloric  peptic  glands.  He 
added,  however,  that  the  differences,  considerable  in  the  rat,  slight  in  the  dog, 
between  the  glands  of  Brunner  and  the  pyloric  glands,  led  him  to  believe  that  their 
secretion  was  not  identical,  but  that  the  glands  of  Brunner  secreted  a  special  digestive 
liquid. 

A  similar  view  of  the  nature  of  the  Brunner's  glands  is  taken  by  von  Ebner 
(1899),  who  bases  his  conclusions  as  to  their  non-mucous  nature  on  the  failure  to  stain 
them  with  Mayer's  mucicarmine  and  muchsematein. 

The  lack  of  unanimity  of  opinion  as  to  the  nature  of  the  glands  of  Brunner  is  to 
be  traced  to  a  number  of  causes.  Of  the  first  importance,  in  this  connection,  is  the 
resemblance  of  the  glands  of  Brunner  to  the  pyloric  glands  of  the  stomach  which 
Heidenhain  (1870,  1878)  and  his  pupils  had  shown,  apparently  conclusively,  on  physio- 
logical grounds,  to  be  pepsin-forming  serous  glands.  This  conclusion,  as  far  as  the 
pyloric  glands  are  concerned,  has  been  shown  to  be  erroneous  by  the  writer  (1896, 
1898)  on  histological  and  microchemical  grounds,  and  for  chemical  reasons  by  Glassner 
(1902),  who  has  confirmed  the  conclusion  of  the  writer  that  the  glands  of  the  pyloric 
region  do  not  contain  pepsin -zymogen  (propepsin).  A  second  cause  which  has  con- 
tributed to  this  confusion  of  results  is  the  lack  of  precision  in  our  morphological 
criteria  for  distinguishing  between  mucous  and  serous  cells.  In  the  absence  of  specific 
knowledge  of  the  chemistry  of  the  secretion  of  a  gland,  a  mucous  gland  in  which 
the  nucleus  was  spherical  and  the  cytoplasm  abundant  would  invariably,  according  to 
the  older  ideas,  be  interpreted  as  a  serous  gland. 

The  classification  of  glands  into  mucous  glands  and  serous  glands  is  at  the  best  a 
mere  makeshift.  When  we  have  decided  that  a  gland  is  a  serous  gland,  we  may  still 
know  absolutely  nothing  about  the  nature  of  its  secretion,  beyond  the  fact  that  it  does 
not  contain  a  mucin.  There  are,  however,  a  number  of  serous  glands  the  secretion  of 
which  it  is  possible  to  collect  and  examine  chemically,  and  which  are  known  to  be 
largely  engaged  in  the  secretion  of  digestive  enzymes.  To  this  category  belong  certain 
of  the  serous  salivary  glands,  the  pancreas,  and  the  chief  cells  of  the  gastric  glands. 
In  recent  years  these  zymogenic  glands  have  been  the  subject  of  numerous  investiga- 
tions, as  a  result  of  which  we  now  have  a  tolerably  exact  knowledge  of  their  structure 
in  the  different  phases  of  physiological  activity.  The  serous  glands  have  been  inves- 
tigated by  Solger  (1894,  1896,  1898),  Erik  Mailer  (1895),  Zimmermann  (1898),  Gar- 
nier  (1900),  and  others;  the  pancreas,  by  Eberth  and  Muller  (1892),  Mouret  (1895), 
Macallum  (1891,  1895,  1898),  and  Matthews  (1899);  the  gastric  glands,  by  Bensley, 
(1896,  1898,  1902),  Zimmermann  (1898),  Theohari  (1899),  and  Cade  (1901). 

These  researches  show  that  serous  glands  which  are  known  to  be  zymogenic  in 
function,  whatever  their  source,  have  certain  features  in  common,  due  to  the  presence 

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6          THE  STBUCTURE  OP  THE  GLANDS  OF  BBUNNEB 

in  the  cell  of  the  several  substances  antecedent  to  the  secretion.  These  are,  briefly, 
the  zymogen  granules  which  occupy  the  portion  of  the  cell  nearest  the  lumen,  and 
which  are  easily  visible  in  the  fresh  cell,  and  the  jwozymogen,  a  nucleoproteid  sub- 
stance probably  of  nuclear  origin,  remarkable  for  its  staining  power,  located  in  the 
base  of  the  cell.  The  latter  substance  is  often  unequally  distributed  in  the  basal  cyto- 
plasm, giving  rise  to  the  appearance  of  radial  striation,  to  which  we  owe  the  name 
"basal  filaments,"  first  employed  for  the  prozymogen  of  the  glandula  submaxillaris  of 
man  by  Solger  (1896). 

Both  of  the  substances  mentioned  above  as  characteristic  constituents  of  the 
zymogenic  cell  give  microchemical  reactions  which  enable  one  to  distinguish  them 
with  some  confidence  from  the  substances  antecedent  to  secretion  in  a  mucous  cell. 
The  fact  that  the  prozymogen  is  a  nucleoproteid  enables  one  to  employ  the  micro- 
chemical  tests  for  iron  and  phosphorus  for  its  identification,  and  no  structure  in  any 
cell  should  be  likened  to  the  basal  filaments  of  the  serous  zymogenic  cell  unless  it  does 
give  a  positive  result  with  these  tests.  Furthermore,  the  granules  of  zymogen  may  be 
positively  distinguished  from  granules  of  mucigen  by  the  fact  that  after  careful 
extraction  with  alcohol  and  ether  in  a  Soxhlet  apparatus  to  remove  the  lecithins,  they 
give  a  strong  reaction  by  Macallum's  method,  showing  the  presence  in  them  of  organic 
phosphorus  as  an  elementary  constituent. 

Mucous  cells,  on  the  other  hand,  do  not  contain  any  basal  filaments,  and  the  feeble 
reaction  for  organic  iron  which  they  give  indicates  that  they  contain  a  relatively  small 
amount  of  diffused  prozymogen.  As  pointed  out  above,  the  secretion  granules  of 
mucous  cells  do  not  give  any  reaction  for  organic  phosphorus. 

In  addition  to  the  above  characters  which  we  can  apply  in  distinguishing  serous 
from  mucous  cells,  we  are  able,  owing  to  the  researches  of  Paul  Mayer  (1896)  on  the 
methods  of  staining  mucus,  to  obtain,  with  much  greater  certainty  than  before,  a 
positive  staining  reaction  for  this  substance  in  cells  by  employing  the  special  solutions 
of  hsematein  and  carmine  devised  by  him. 

Up  to  the  present,  there  has  been  no  attempt  to  apply  these  methods  to  the  study 
of  the  glands  of  Brunner.  We  must,  therefore,  compare  these  glands  as  regards  the 
structure,  staining  and  microchemical  reactions,  and  the  changes  exhibited  by  them  in 
different  phases  of  functional  activity,  not  only  with  the  nearly  adjacent  gastric  and 
intestinal  glands,  but  also  with  the  many  glands  from  other  sources  which  have  been 
the  subject  of  exact  investigation. 

A  point  on  which  most  writers  agree  is  the  great  similarity  between  the  glands  of 
Brunner  and  the  pyloric  glands  of  the  stomach,  although  recent  researches  of 
Kuczynski  (1890),  Castellant  (1898),  and  others  do  not  confirm  the  conclusions  of 
Bentkowski  (1876)  and  Schiefferdecker  (1884)  that  the  two  sorts  of  glands  are  iden- 
tical. 

The  question  of  the  relationship  of  the  glands  of  Brunner  to  the  pyloric  glands 
is  mainly  interesting  from  the  standpoint  of  the  phylogenesis  of  the  former.  Although 

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ROBERT  RUSSELL  BENSLEY 


they  occur  for  the  first  time  in  mammals,  the  fact  that  they  have  been  found  without 
exception  in  all  mammals  belonging  to  the  three  main  subclasses  in  which  they  have 
been  sought,  indicates  that  they  must  have  appeared  very  early  in  the  history  of  the 
Mammalia.  The  fact  that  the  pyloric  glands  and  the  Brunner's  glands  have  been 
subject  throughout  this  long  phylogenetic  history  to  conditions  which  are  not  identical 
would  alone  be  sufficient  to  explain  slight  differences  in  the  nature  of  their  cells,  even 
if,  as  some  suspect,  the  two  sets  of  glands  have  had  a  common  origin.  Furthermore, 
in  many  groups  of  animals,  owing  to  a  change  of  food  habits,  the  stomach  has  under- 
gone important  secondary  adaptive  modifications,  resulting  in  the  suppression  of 
extensive  areas  of  gastric  glands,  the  replacement  of  the  cylindrical  epithelium  by  a 
stratified  squamous  epithelium,  and  the  modification  in  type  of  the  remaining  glands. 
It  is  reasonable  to  expect  that,  under  these  extraordinary  conditions,  the  pyloric  glands 
would  be  modified,  and  the  differences  between  them  and  Brunner's  glands  intensified. 
Clearly,  it  would  be  unfair  to  assume  that,  because  the  pyloric-gland  cells  differ  from 
those  of  Brunner's  glands  in  an  animal  with  such  a  specialized  stomach,  they  are 
primitively  different.  In  other  words,  in  discussing  the  question  of  the  difference  or 
similarity  of  the  two  sets  of  glands,  both  the  long  phylogenetic  history  of  the  glands 
and  the  relative  visceral  specialization  of  the  animal  under  discussion  must  be  given 
due  weight. 

The  present  memoir  embodies  the  results  of  an  investigation  undertaken  with  a 
view  of  applying  to  the  solution  of  the  problems  presented  by  the  glands  of  Brunner 
the  microchemical  and  staining  methods  employed  by  the  writer  in  the  stiidy  of  the 
glandular  elements  of  the  stomach,  and  the  more  recent  conception  of  the  structure 
of  these  and  other  cells.  With  this  end  in  view,  the  glands  of  Brunner  of  one  mar- 
siipial  and  of  nineteen  placental  species  representing  six  orders  of  mammals  have 
been  submitted  to  a  careful  anatomical  and  histological  examination.  The  results 
from  a  phylogenetic  standpoint  are  somewhat  disappointing,  but  it  is  hoped  that 
they  will  bring  us  nearer  to  a  proper  conception  of  the  morphology  of  the  glands  in 
question. 

The  material  for  study  included  the  pyloric  glands  and  glands  of  Brunner  of  the 
opossum,  dog,  cat,  mink  (Lutreola),  raccoon  (Procyon),  hedgehog  (Erinaceus),  por- 
cupine (Erethizon),  guinea  pig,  ground  hog  (Arctomys  monax),  squirrel,  rabbit, 
dormouse  (Muscardinus  avellanarius),  muskrat  (Fiber  zibethicus),  mouse,  rat,  deer 
mouse  (Peromysciis),  sheep,  pig,  and  man. 

The  glands  of  Brunner  of  the  opossum  have  been  selected  for  the  preliminary 
description,  because  the  shape  and  structure  of  the  stomach  in  this  form  correspond 
so  closely  to  those  which  we  have  reason  to  believe  were  primitive  in  mammals  that 
we  may  expect  to  find  primitive  conditions  in  the  glands,  and  because  the  peculiar 
characteristics  of  the  glands  of  Brunner  in  the  opossum  furnish,  it  is  thought,  the 
strongest  argument  which  could  be  brought  forward  in  favor  of  the  theory  that  they  are 
produced  directly  from  the  pyloric  glands. 

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THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNEB 


IF.    THE  GLANDS  OF  BRUNNER  OP  DIDELPHYS  VIRGINIANA 

The  glands  of  Brunner  in  the  opossum  form  a  narrow  ring  around  the  pyloric 
orifice  of  the  stomach.  In  a  preparation  of  the  stomach  and  duodenum,  cut  open 
along  the  line  of  attachment  of  the  hepatogastric  and  hepatoduodenal  ligaments,  one 
may  see  in  the  mucous  membrane  at  the  gastro-diiodcnal  junction  with  a  low  magnifica- 
tion, a  number  of  minute  funnel-shaped  depressions,  forming  two  or  three  irregular 
rows  more  or  less  parallel  with  the  line  of  junction  of  the  stomach  and  intestine,  and 
at  distances  of  two  to  three  millimeters  apart.  On  examination  in  sections  these  prove 
to  be  the  openings  of  tubular  depressions  of  the  mucous  membrane  into  which 
the  glands  of  Brunner  open.  These  depressions  are  not,  however,  in  the  strict  sense, 
the  ducts  of  the  glands,  but  rather  evaginations  of  the  mucous  membrane  as  a  whole, 
because,  in  the  inner  portions  of  them,  villi  project  from  the  wall  into  the  cavity,  and 
small  intestinal  glands  occur,  beneath  which  a  continuation  of  the  longitudinal  fibers 
of  the  lamina  muscularis  mucosse  may  be  seen.  These  intestinal  elements  may  be 
traced  to  a  short  distance  below  the  level  of  the  lamina  muscularis  mucosse  of  the 
stomach  and  intestine,  where  the  depression  opens  into  a  cavity  of  considerable  size, 
around  which  the  lobules  of  the  glands  of  Brunner  are  clustered,  and  into  which  the 
ducts  of  the  latter  open.  If  the  stomach  and  intestine,  and  after  ligation  of  the  latter 
some  inches  below  the  pylorus,  be  distended  with  the  fixing  fluid,  under  sufficient  pres- 
sure to  overcome  the  resistance  of  the  pyloric  sphincter  and  to  dilate  the  opening  to  a 
width  of  about  1.5  cm.,  one  sees  at  the  gastro-duodenal  junction,  instead  of  the  depres- 
sion referred  to  above,  a  number  of  rounded  patches  which  are  smooth  and  devoid  of 
villi.  In  sections  of  such  a  preparation,  the  appearance  represented  in  Plate  XIX, 
Fig.  1  is  observed ;  the  lobules  of  the  glands  of  Brunner  are  clustered  around  a  place 
where  the  ordinary  elements  of  the  intestinal  mucous  membrane  are  lacking  and  only 
an  epithelium  is  to  be  seen.  Through  large  openings  in  this  epithelium  empty  the 
ducts  of  the  glands  of  Brunner.  The  first  row  of  these  defects  in  the  intestinal  mucous 
membrane  occurs  at  or  near  the  gastro-duodenal  junction,  that  is  to  say,  the  first  row 
of  patches  into  which  the  glands  of  Brunner  open  may  be  continuous  with  the  mucous 
membrane  of  the  stomach,  or  may  be  separated  from  the  latter  by  a  minute  interval, 
about  O.lmm.  in  width,  in  which  villi,  intestinal  glands,  etc.,  may  be  found.  In  the 
former  case,  the  glands  of  Brunner  have  the  appearance  of  being  a  continuation  of  the 
pyloric  glands;  in  the  latter,  they  appear  to  be  entirely  separated  from  them.  • 

The  extent  of  the  glands  of  Brunner  in  a  longitudinal  direction  is  about  6.7  mm., 
beginning  about  1.2  mm.  above  the  point  where  the  gastric  and  duodenal  epithelium 
meet,  and  extending  a  distance  of  5mm.  to  5.5mm.  into  the  tela  submucosa  of  the 
duodenum.  They  form  a  series  of  angular  lobules,  some  entirely  separate,  others 
aggregated  into  larger  or  smaller  lobes. 

The  glands  are  of  a  branched  acinotubular  type.  The  smaller  lobules  have  as  a 
rule  a  single  tubular  duct  which  opens  on  the  surface  of  one  of  the  depressions  above 

284 


ROBERT  RUSSELL  BENSLEY  9 

described.  This  duct  penetrates  to  the  center  of  the  lobule  giving  off  radial  tubular 
branches  which  subdivide  repeatedly  until  an  exceedingly  complex  structure  is  pro- 
duced. All  tubules  below  the  main  duct  give  off  at  frequent  intervals  short  tubules 
which  are  regarded  by  Maziarski  (1902)  as  acini.  The  cells  lining  all  these  branches 
of  the  main  duct,  and  indeed  those  of  a  large  portion  of  the  duct  itself,  are  of  precisely 
the  same  character. 

The  tubules  are  surrounded  and  supported  by  the  collagenic  connective  tissue  of 
the  tela  submucosa,  in  which  may  be  seen  near  the  epithelium  of  the  defect  small 
strands  of  smooth  muscle  fiber  which  represent  the  remains  of  the  lamina  muscularis 
mucosse.  In  the  tissue  between  the  glands  numerous  mast  cells  may  be  seen,  some 
lying  free  in  the  connective  tissue,  others  closely  applied  to  the  outer  surface  of  the 
glandular  epithelial  cells. 

The  defect  of  the  tunica  mucosa,  into  which  the  ducts  of  the  glands  open,  is  cov- 
ered by  a  single  layer  of  epithelial  cells.  At  the  edge  of  the  patch  these  consist  of  the 
usual  epithelial  elements  of  the  intestine,  namely  goblet  cells,  cylindrical  epithelial 
cells  with  basal  cuticula,  and  granule  cells  of  Paneth.  Epithelium  of  this  character, 
however,  extends  over  a  very  small  portion  of  the  extreme  margin  of  the  patch  and  is 
broken  by  only  a  few  ducts.  The  greater  portion  of  the  area  is  covered  by  cylindrical 
epithelial  cells  of  the  mucigenous  type.  The  shape  and  dimensions  of  these  surface 
epithelial  cells  vary  within  wide  limits,  according  to  the  tension  and  shape,  that  is, 
convexity  or  concavity,  of  the  surface  upon  which  they  rest.  On  relaxed  portions  of 
the  surface,  they  are  very  high  and  narrow,  17-27  /*  in  height  by  5-7  /*  in  width.  If, 
however,  the  tissue  is  fixed  under  tension,  they  appear  short  and  wide  and  the  position 
and  shape  of  the  nucleus  are  similarly  modified. 

At  first  sight  the  resemblance  of  the  epithelium  to  that  of  the  stomach  is  remark- 
able, but  on  close  examination  it  is  foiind  that  this  resemblance  does  not  amount  to 
identity,  although  the  differences  are  not  of  great  importance.  As  in  the  gastric  epi- 
thelium, the  distal  portion  of  the  cell  is  occupied  by  a  mass  of  secretion  forming  a  dis- 
tinct theca.  The  proximal  portion  of  the  cell  is  occupied  by  finely  reticular  cytoplasm 
and  contains  an  oval  nucleus.  The  latter  may  be  slightly  flattened  where  it  comes  into 
contact  with  the  mass  of  secretion.  The  differences  between  these  cells  and  those  of 
the  gastric  epithelium  are  particularly  emphasized  in  specimens  stained  in  iron  alum 
hffimatoxylin,  in  muchsematin,  or  in  mucicarmine.  In  the  former  stain  the  theca  of  the 
gastric  epithelial  cell  appears  of  a  slightly  grayish  color  and  homogeneous.  The 
masses  of  mucin  (granules?)  which  fill  the  theca  are  so  closely  aggregated  that  there  is 
but  little  cytoplasm  left  in  the  free  ends  of  the  cell  to  retain  the  stain.  At  the  base  of 
the  theca  only,  can  be  made  out  a  delicate  network,  which  extends  from  the  cytoplasm 
between  the  theca  and  the  nucleus  for  a  short  distance  into  the  mass  of  secretion.  In 
the  epithelial  cells  of  the  Bruunerian  area,  on  the  other  hand,  the  theca  is  subdivided 
by  delicate  strands  of  cytoplasm  forming  a  network  in  the  meshes  of  which  the 
granules  of  mucin  are  lodged.  Moreover,  the  theca  is  subdivided  into  proximal  and 

285 


10          THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNEB 

distal  portions  by  incomplete  bands  of  cytoplasm,  stretching  across  it,  parallel  with  the 
free  border  of  the  cell.  The  meaning  of  these  facts  will  be  discussed  later.  In  the 
meantime  it  is  merely  intended  to  point  out  that  the  theca  of  the  epithelial  cells  under 
discussion  contains  a  larger  proportion  of  cytoplasmic  elements,  as  distinct  from  stored- 
up  secretion,  than  that  of  the  epithelium  of  the  stomach.  A  further  point  of  differ- 
ence is  to  be  seen  in  the  size  of  the  theca,  which  presents  a  remarkable  uniformity  in 
the  gastric  epithelium,  but  is  very  variable  in  the  epithelium  of  the  defects. 

Toward  the  bottom  of  the  gastric  foveolae,  however,  cells  are  found  which  agree 
very  closely  in  structure  with  the  cells  of  the  defects,  and  these,  as  has  been  frequently 
pointed  out,  by  Bizzozero  (1893)  and  others,  are  connected  with  the  cells  of  the  sur- 
face by  a  gradual  transition.  A  similar  transition  may  be  seen  at  the  gastro-duodenal 
junction,  where  the  epithelium  of  one  of  the  defects  happens  to  be  continuous  with  the 
gastric  epithelium.  We  may  therefore  conclude  that  the  epithelium  of  the  defects  is 
gastric  epithelium  not  so  highly  differentiated  as  that  of  the  surface  of  the  stomach. 

The  ducts  which  open  on  the  defects  are  lined  for  a  greater  or  less  portion  of 
their  course  by  epithelium  of  the  type  described  above,  except  that  the  cells  are  as  a 
rule  shorter  and  wider  than  on  the  free  surface.  At  variable  distances  from  the  open- 
ing of  the  duct,  there  is  transition,  sometimes  abrupt,  sometimes  gradual,  to  the  glan- 
dular epithelium  which  lines  all  the  numerous  side  and  terminal  branches  of  the  gland. 

The  two  animals  from  which  the  material  was  obtained  exhibited  different  physio- 
logical phases  of  the  gland ;  in  one  the  cells  were  completely  filled  with  secretion,  in 
the  other  only  partly  so.  A  transverse  section  of  two  tubules  from  the  latter  animal 
is  represented  in  Plate  XX,  Fig.  2.  Each  tubule  is  composed  of  somewhat  rec- 
tangular cells,  very  similar  in  general  characters,  but  with  some  differences  of  detail, 
surrounding  a  central  cavity.  The  lumen  varies  in  width  from  4/i  to  16/4,  the  largest 
diameter  being  usually  found  in  the  main  branches  of  the  duct  and  in  those  terminal 
tubules  (acini)  which  lie  at  the  margin  of  a  lobule.  In  each  glandular  cell  a  number  of 
distinct  zones  may  be  made  out.  Beginning  at  the  outside  of  the  tubule  and.  proceed- 
ing toward  the  lumen,  there  may  be  distinguished,  first,  a  narrow  zone  of  cytoplasm,  of 
a  delicate  reticular  structure,  stretching  across  the  base  of  the  cell  and  containing  the 
somewhat  irregular  nucleus.  On  the  distal  side  of  the  nucleus  a  clear  zone  with  coarse 
reticular  structure  may  be  observed,  then  a  narrow  band  of  finely  reticular  cytoplasm, 
and  finally  a  second  coarsely  reticular  clear  zone,  bordering  the  lumen.  The  meshes 
of  the  two  clear  zones  obviously  contain  the  stored-up  secretion  of  the  cells,  which  is 
divided  into  a  proximal  and  a  distal  mass  by  the  transverse  bridge  of  cytoplasm.  This 
reciprocal  arrangement  of  the  cytoplasm  and  its  product  is  deserving  of  some  emphasis 
because  of  the  fact  that  it  occurs  with  surprising  constancy  in  corresponding  phases  of 
secretion  in  mucous  cells  from  the  most  varied  sources,  e.  g.,  salivary,  palatine,  ceso- 
phageal,  and  tracheal  glands,  the  cardiac  and  pyloric  gland  cells  of  the  stomach,  and 
the  neck  chief  cells  of  the  fundus  glands.  Zimmermann  (1898)  observed  this  struc- 
ture in  the  cells  of  the  human  glands  of  Brunner,  but  did  not  attempt  an  interpreta- 

286 


ROBERT  RUSSELL  BENSLEY  11 

tion.  Kolossow  (1898),  by  means  of  his  osmic-acid  reduction  method,  obtained  similar 
pictures  in  the  salivary  glands,  and  recently  Maximow  (1901)  has  demonstrated  it  by 
thionin  staining  in  the  mucous  salivary  glands.  The  writer  has  repeatedly  called  atten- 
tion to  this  phenomenon  in  the  mucous-secreting  cells  of  the  stomach.  A  character 
which  reappears  with  such  constancy  in  similar  cells  from  so  many  different  sources 
must  have  a  very  important  significance. 

The  network  which  is  visible  in  the  clear  zones  of  these  cells  is  neither  a  true 
cytoplasmic  reticulum  (spongioplasma)  nor  an  alveolar  structure  (Wabenstructur), 
but  is  probably  a  derivative  of  the  latter.  In  sections  stained  intensely  in  iron  alum 
hsematoxylin  it  is  possible  to  follow  the  threads  of  the  network  by  focusing.  In  such 
preparations  it  is  seen  that,  in  a  great  many  cases,  they  are  not  fibers,  as  would  appear 
at  first  sight,  but  thin  laminae  which  intersect  and  join  to  form  the  visible  network. 
The  spaces  of  this  network  are,  however,  everywhere  continuous  with  one  another. 
Often,  however,  the  proximal  mass  of  secretion  near  the  nucleus  exhibits  a  true  alveo- 
lar structure,  the  spaces  being  rounded  cavities  containing  reserve  secretion,  separated 
completely  from  one  another  by  the  continuous  cytoplasm  of  the  zone.  It  is  easily 
conceivable  that  the  latter  structure  has  given  rise  to  the  former  by  the  increase  in 
size  and  partial  coalescence  of  the  small  secretion  spaces.  Usually  there  is  a  very 
obvious  difference  in  the  amount  of  residual  cytoplasm  contained  in  the  proximal  and 
in  the  distal  clear  zones  respectively,  the  proximal  zone  exhibiting  smaller  spaces  and 
larger  cytoplasmic  trabeculae  than  the  distal  zone. 

The  cytoplasm  of  these  cells  does  not  contain  basal  filaments,  but  the  presence  of 
a  small  amount  of  cytoplasmic  nucleoproteid  is  indicated  by  the  feeble  but  positive 
reactions  for  iron  obtained  by  Macallum's  methods. 

In  order  to  study  under  the  best  conditions  the  reciprocal  relations  of  the  cyto- 
plasm and  secretion,  it  was  necessary  to  have  an  intense  stain  of  the  masses  of  secre- 
tion, leaving  the  cytoplasm  unstained.  The  various  synthetic  dyes  which  were  tried 
did  not  yield  very  satisfactory  results,  as,  although  a  positive  result  was  obtained  with 
thionin,  toluidin  blue,  and  methyl  blue,  the  stain  was  not  sufficiently  selective  to  per- 
mit of  accurate  definition  of  the  cytoplasm  and  secretion  respectively.  By  means  of 
P.  Mayer's  muchsematein  the  writer  obtained  a  very  intense  and  satisfactory  stain  of 
the  secretion  by  transferring  thin  sections  cut  in  paraffin,  from  benzole  to  absolute 
alcohol,  and  then  to  the  stain,  but  was  unsuccessful  with  similar  sections  fastened  to 
the  slide.  It  was  subsequently  found  that,  by  gradually  increasing  the  strength  of  the 
solution  without  altering  the  relative  proportions  of  its  solid  constituents,  a  solution 
was  obtained  which  could  be  used  for  staining  sections  fastened  to  the  slide,  with  cer- 
tainty of  speedy  and  satisfactory  results.  The  procedure  is  as  follows :  The  stain 
consists  of  hsematein,  1  g.,  aluminium  chloride,  0.5  g.,  70  per  cent,  alcohol,  100  c.c. 
The  hfflmateiu  and  chloride  are  rubbed  up  together  in  a  mortar,  then  mixed  with  the 
alcohol,  the  whole  being  allowed  to  stand  a  week  to  insure  perfect  ripeness  of  the  solu- 
tion. During  this  week  the  solution  deepens  in  color,  and  its  staining  power  for  mucin 

287 


12          THE  STRUCTURE  OF  THE  GLANDS  OF  BBUNNER 

increases  daily.  The  sections  fastened  to  the  slide  by  the  water  method  are  treated 
with  benzole  and  absolute  alcohol.  The  slide  is  then  flooded  with  the  staining  solution, 
placed  on  the  stage  of  the  microscope,  and  watched  until  the  intense  blue  color  appears 
in  the  cells.  The  sections  are  then  rapidly  washed  in  95  per  cent,  alcohol,  dehy- 
drated, cleared,  and  mounted  in  xylol  balsam.  Washing  in  water  extracts  the  stain, 
but  if  the  sections  are  first  washed  in  70  per  cent,  alcohol,  then  in  lime  water,  the 
stain  is  fixed,  and  subsequent  washing  in  water  affects  it  but  slowly.  Similarly 
effective  results  may  be  obtained  with  mucicarmine,  if  the  strong  stock  solution  of 
Mayer  be  employed  instead  of  the  diluted  solution.  Mucicarmiue  can  be  depended  on 
only  if  the  solution  is  freshly  prepared ;  the  old  solutions  do  not  give  satisfactory 
results.  The  stain  obtained  with  mucicarmine  is  very  stable,  is  not  affected  by  washing 
in  water,  and  may  be  used  for  subsequent  contrast  staining.  Very  excellent  double 
stains,  remarkably  rich  in  detail,  are  obtained  by  staining  in  iron  alum  htGinatoxylin, 
followed  by  mucicarmine. 

Muchsematein,  prepared  and  applied  in  the  way  described  above,  gives  an  intense 
blue  color  to  the  contents  of  the  goblet  cells  and  of  the  clear  portion  of  the  glandular 
epithelial  cells  of  Brunner.  Old  solutions  stain  the  granules  of  the  mast  cells  and,  if 
the  solutions  are  acid,  as  Harris  has  pointed  out,  the  coarser  elastic  fibers.  Cytoplasm 
remains  unstained.  Cells  stained  in  this  way  exhibit  the  exact  reverse  of  the  struc- 
ture described  above,  and  illustrated  in  Fig.  2.  The  clear  zones  of  the  cell  appear 
filled  with  deeply  stained  secretion,  the  rest  of  the  cell  colorless. 

Considerable  interest  attaches  to  the  mode  of  aggregation  of  the  secretion  in  the 
cell,  and  in  this  connection  some  results  have  been  obtained  which  afford  a  simple 
explanation  of  the  discordant  results  on  the  mucous  salivary  glands.  The  writer  was 
at  first  considerably  puzzled  by  the  fact  that  in  some  of  his  preparations  the  secretion 
appeared  in  the  form  of  distinct  granules,  in  others  in  the  form  of  a  continuous  coarse 
meshed  network.  It  was  speedily  found,  however,  that  if  water  were  excluded  from 
the  operations  of  the  technique,  the  granular  condition  was  always  obtained,  whereas 
if  water  were  introduced  at  any  stage,  the  reticular  appearance  was  obtained.  For 
example,  sections  stained  without  fastening  to  the  slide,  or  after  cutting  in  celloidin, 
by  simply  transferring  from  strong  alcohol  to  the  stain,  then  back  to  alcohol,  gave 
granules ;  sections  passed  through  water,  or  fastened  to  the  slide  by  the  water 
method  and  heat,  gave  a  network.  The  obvious  inference  was  that  the  secretion  was 
stored  in  the  cells  in  the  form  of  fine  granules  or  droplets  which  had  not  been  altered 
chemically  by  the  fixing  agents,  and  which  on  treatment  with  water  promptly  went 
into  complete  or  partial  solution,  to  be  again  precipitated  by  the  stain  in  reticular 
form.  It  is  a  well-known  fact  that  mucins  outside  the  cell  precipitate  frequently  in 
the  form  of  a  coarse  network. 

We  may  now  return  to  a  description  of  the  cell  after  staining  with  mucliBB- 
matein  in  such  a  way  as  to  preserve  the  granules  of  secretion.  Such  a  preparation  is 
illustrated  in  Plate  XX,  Fig.  3.  In  each  cell  there  are  seen  to  be  two  masses  of 

288 


ROBERT  RUSSELL  BENSLEY  13 

granules  corresponding  to  the  two  clear  zones  of  the  cells  of  the  preceding  figure. 
The  granules  in  the  distal  mass  bordering  on  the  lumen  are  very  closely  aggregated, 
very  small,  and  somewhat  angular  in  outline.  Those  of  the  proximal  mass  are  less 
closely  packed,  often  somewhat  scattered,  smaller  and  more  rounded. 

If  we  now  combine  the  results  of  the  two  methods  of  staining,  we  may  conceive 
the  clear  secretion-filled  zones  of  the  fixed  cell  to  be  composed  of  two  elements,  strands, 
threads,  and  delicate  laminae  of  cytoplasm,  forming  a  network,  in  the  meshes  of  which 
are  minute  granules  of  secretion,  the  latter  separated  from  one  another,  sometimes  by 
the  threads  of  cytoplasm,  more  often  by  clear  spaces.  This  appearance  may  be  inter- 
preted in  one  of  two  ways.  In  the  living  cell  the  granules  of  secretion  must  be  sepa- 
rated from  one  another  by  a  continuous  substance  of  some  kind.  This  continuous 
separating  substance  may  be  either  the  cytoplasm  or  a  third  substance  of  a  more 
watery  nature,  filling  the  interstices  of  the  cell  between  the  particles  of  secretion  and 
the  cytoplasm.  In  the  former  case  the  strands  of  cytoplasm  seen  in  the  dead  cell 
would  represent  merely  the  contracted  precipitates  produced  in  the  continuous  cyto- 
plasm by  the  fixing  reagents ;  in  the  latter  case  they  would  represent  the  actual  distri- 
bution of  the  cytoplasm  in  the  living  cell.  The  latter  interpretation  seems  the  more 
probable  for  a  number  of  reasons.  In  the  first  place,  it  suggests  a  possible  explanation 
of  the  capacity  of  the  cell  to  vary  the  respective  constituents  of  its  secretion  in  response 
to  specific  stimuli,  the  possibility  of  which  has  been  clearly  demonstrated  by  the  work 
of  Pawlow  (1898)  and  his  pupils  on  the  stomach,  and  by  that  of  Malloisel  (1902)  on 
the  submaxillary  gland.  In  the  second  place,  one  frequently  sees  granules  with  minute 
threads  of  substance  stainable  in  mucha3matein  projecting  from  their  surfaces  suggest- 
ing that  there  is  an  intermediate  clear  substance  (the  hyaline  substance  of  Langley) 
in  which  portions  of  the  secretion  of  the  cell  exist  in  complete  solution.  A  third  reason, 
perhaps  a  stronger  one  than  either  of  the  two  foregoing,  is  that  one  finds  the  secretion  in 
the  form  of  droplets  or  granules  in  the  theca  of  goblet  cells  from  some  sources,  in  which 
strong  staining  in  iron  hsematoxylin  shows  the  presence  of  only  faint,  delicate  threads 
of  cytoplasm,  or  of  none  at  all. 

A  glandiilar  tubule  from  a  section  fastened  to  the  slide  by  the  usual  water  method 
and  stained  in  muchsematein  is  represented  in  Plate  XXI,  Fig.  8.  The  granules  of 
secretion  have  disappeared  and  have  given  place  to  the  coarse  network  usually  seen  in 
mucous  cells.  The  division  of  the  accumulated  secretion  into  an  inner  and  an  outer 
mass  may  still  be  recognized  in  some  of  the  cells,  although  the  bridge  of  protoplasm 
separating  these  is  less  obvious  in  the  midst  of  the  deeply  stained  secretion.  This  net- 
work again  is  not  of  an  alveolar  character,  as  the  laminae  and  trabeculae  which  form  it 
are  perforated  and  interrupted  in  such  a  way  that  the  clear  spaces  throughout  the 
mass  communicate  with  one  another. 

The  blue-stained  network  observed  in  muchsematein  preparations  is  a  precipitation 
product,  and  must  not  be  confused  with  the  network  visible  in  the  clear  zones  of  cells 
stained  by  the  iron-haematoxylin  method.  The  mucinoid  material  is  doubtless  precipi- 

289 


14          THE  STRUCTURE  OF  THE  GLANDS  OF  BBUNNER 

tated  in  part  on  the  cytoplasmic  meshes,  but  not  wholly  so,  because  the  network  obtained 
in  muchaemateiu  is  formed  by  much  larger,  coarser  meshes  than  that  seen  in  the  iron 
haematoxylin  preparation.  Moreover,  one  may  completely  remove  the  substance  stain- 
able  in  muchsematein  by  treatment  of  the  sections  for  several  hours  with  a  dilute  solu- 
tion of  barium  hydroxide.  Subsequent  staining  in  iron  hsematoxylin  shows  that  the 
cytoplasmic  network  in  the  clear  zones  of  the  cell  has  undergone  no  change. 

We  may  now  consider  the  changes  exhibited  by  the  cell  while  passing  from  the 
intermediate  state  described  in  the  foregoing  paragraph  to  the  fully  loaded  conditions. 
As  already  pointed  out,  one  may  find  in  the  same  tubule  cells  in  the  different  secretory 
conditions,  and  by  comparing  cells  from  different  tubules  an  idea  may  be  obtained  of 
their  secretory  phases.  The  majority  of  the  cells  in  Fig.  2  are  in  a  condition  inter- 
mediate between  the  loaded  and  the  discharged  states.  The  completely  loaded  stage 
is  represented  in  Plate  XX,  Fig.  4,  drawn  from  a  tubule  of  a  gland  of  Brunner  of  a 
second  opossum,  stained  with  iron  hasmatoxylin.  In  this  preparation  the  cell  presents 
a  swollen  aspect  and  exhibits  throughout  a  coarse  meshwork  of  cytoplasm  inclosing  clear 
secretion  spaces.  There  is  no  indication  of  a  subdivision  of  the  contained  secretion 
into  a  proximal  and  distal  mass,  the  transverse  bridge  of  protoplasm  seen  in  most  of 
the  cells  of  Fig.  2  being  here  represented  only  by  a  slight  thickening  of  some  of  the 
cytoplasmic  trabecula?  in  the  middle  of  the  cell.  The  cytoplasm  at  the  base  of  the 
cell,  which  was  of  considerable  extent  in  Fig.  2,  is  here  reduced  to  a  minimum,  and 
the  nucleus  has  in  many  cells  taken  on  the  crescentic  form  so  characteristic  of  mucous 
cells.  The  tubules  of  the  gland  in  this  individual  were  in  general  larger  and  the  lurnina 
narrower  than  in  those  from  the  first  animal.  An  idea  of  the  way  in  which  this  secretion- 
loaded  cell  is  derived  from  those  of  the  type  illustrated  in  Fig.  2  may  be  gained  by 
studying  a  large  number  of  tubules  from  the  same  animal  stained  in  iron  hsematoxylin 
and  in  muchsematein.  It  has  been  pointed  out  that  in  preparations  stained  with 
muchasmatein  without  coming  in  contact  with  water  the  secretion  appears  in  the  form 
of  rounded  granules  arranged  in  two  more  or  less  distinct  groups,  and  that  the  gran- 
ules of  the  proximal  mass  are  frequently  smaller  and  less  crowded  than  those  of  the 
distal  mass.  The  changes  in  the  cell  in  the  act  of  storing  up  secretion  seem  to  be 
going  on  more  actively  in  this  inner  mass  of  granules  which  increases  progressively  in 
density  and  extent  by  increase  in  the  size  of  the  granules  and  by  addition  of  new 
granules.  Correlated  with  this  increase  in  amount  and  number  of  the  droplets  of 
secretion  is  a  diminution  of  the  amount  of  cytoplasm  which  takes  place  simultaneously 
in  the  basal  cytoplasm,  in  that  of  the  transverse  bridge,  and  in  that  of  the  inter- 
granular  trabeculae.  The  result  is  that  the  transverse  bridge  of  cytoplasm  presently 
disappears  and  the  two  masses  of  secretion  become  continuous.  At  the  same  time  the 
amount  of  secretion  in  the  distal  zone  is  probably  increasing,  although  this  is  less 
easily  made  out.  A  comparison  of  the  cells  in  the  two  extreme  conditions  stained  in 
iron  hsematoxylin  shows  that  the  cytoplasmic  network  of  the  distal  zone  is  composed 
of  larger  meshes  in  the  fully  loaded  cell. 

290 


KOBEKT  RUSSELL  BENSLEY  15 

A  feature  of  some  interest  is  the  relation  of  the  granules  of  secretion,  as  seen  in 
muchsematein  preparations,  to  the  nucleus  of  the  cell.  Frequently  only  one  of  the  two 
masses  above  described  may  be  seen,  namely  that  which  corresponds  to  the  proximal  mass, 
the  edge  of  the  cell  along  the  lumen,  in  this  case  being  cy  toplasmic  in  nature.  The  obvious 
interpretation  of  this  fact  is  that  at  the  last  period  of  activity  this  cell  has  thrown  out 
all  of  its  reserve  secretion  and  that,  while  this  has  been  going  on,  the  cytoplasm  has 
been  increasing  in  amount  and  new  granules  have  been  forming  in  the  proximal  seg- 
ment of  the  cell  between  the  nucleus  and  the  mass  of  old  secretion.  In  the  majority 
of  cells,  however,  only  a  portion  of  the  reserve  secretion  is  so  discharged  and  new 
granules  are  deposited  alongside  of  the  old  ones  in  the  interior  of  the  cell. 

The  formation  of  new  secretion  in  mucin-forming  cells  in  close  proximity  to  the 
nucleus  has  been  observed  by  Krause  (1895)  in  the  cells  of  the  retrolingual  gland  of 
Erinaceus,  and  more  recently  has  been  demonstrated  by  Maximow  (1901)  in  the  cells 
of  the  retrolingual  gland  of  the  dog.  The  meaning  of  this  phenomenon  is  not  clear, 
for  although  Carlier  (1899)  has  demonstrated  in  the  large  mucous  cells  of  the  gastric 
glands  of  the  newt,  morphological  changes  of  the  nucleus  in  the  different  phases  of 
secretion  identical  with  those  exhibited  by  the  pepsin-forming  cells,  yet  microchemical 
study  does  not  reveal  in  mucous  cells,  as  it  does  in  many  serous  cells,  the  presence  in  the 
cytoplasm  in  large  amount  of  an  undoubted  product  of  nuclear  activity  (prozymogen, 
ergastoplasm  of  Cade  and  Crarnier).  It  is  possible  that  the  transformation  of  the 
substances  received  by  the  cell  into  mucin  is  accomplished  by  the  agency  of  an  enzyme 
formed  in  the  nucleus.  A  further  possibility  is  the  effect  of  the  presence,  in  relation 
with  the  proximal  mass  of  secretion  of  the  canals  of  Holmgren's  trophospongium, 
although  I  have  not  yet  been  able  to  demonstrate  such  canals  in  the  cells  of  the  glands 
of  Brunner. 

If  one  compares  the  foregoing  description  of  the  cells  of  the  glands  of  Brunner 
with  the  account  of  the  cells  of  the  retrolingual  gland  of  the  dog,  recently  published 
by  Maximow  (1901),  he  cannot  fail  to  be  struck  by  the  extraordinary  resemblance, 
extending  even  to  the  minutest  details,  between  these  two  kinds  of  glands.  In  fact, 
if  we  leave  out  of  account  the  serous  tubules  and  cells  of  the  retrolingual  gland,  the 
description  would  apply  equally  well  to  both.  In  the  case  of  the  glands  of  Brunner, 
it  is  not  possible  to  collect  the  secretion  as  it  flows  from  the  gland  and  examine  it 
chemically,  but  there  are  many  reasons  for  supposing  it  to  consist,  like  that  of  the 
retrolingual  gland,  largely  of  mucin.  These  reasons  are  briefly:  (1)  the  strong 
resemblance  in  structure  and  physiological  phases  to  cells  known  to  be  engaged  in  the 
secretion  of  mucin,  e.g.,  glandula  sublingualis  of  the  dog  ;  (2)  the  stain,  obtained  in 
strong  muchsematein  and  mucicarmine,  in  which  the  protoplasm  of  the  cylindrical, 
intestinal  epithelium  cells  and  the  granules  of  the  cells  of  Paneth  remain  colorless  ; 
the  feeble  metachromatic  stain  occasionally  obtained  in  thionin ;  and  (3)  the  solubility 
in  weak  alkaline  solutions.  The  latter  fact  I  have  established  by  using  muchsematein 
as  an  indicator.  I  found  that  if  sections  attached  to  the  slide  were  treated  with  a  5 

291 


16          THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNEB 

per  cent,  solution  of  potassium  carbonate,  or  a  saturated  solution  of  barium  hydroxide, 
the  substance  in  the  cells  of  the  glands  of  Brunner  slowly  dissolved.  The  various 
stages  of  this  slow  solution  could  be  determined  by  treating  sections  from  time  to  time  with 
strong  muchaematein.  The  procedure  is  as  follows  :  A  number  of  sections  fastened  to 
slides  by  the  water  method  are  freed  from  paraffin,  passed  through  alcohol  to  water, 
placed  in  a  Coplin  jar  containing  a  quantity  of  the  solution  to  be  tested  and  the  whole 
placed  in  an  incubator  at  37°  C.  From  time  to  time  slides  are  removed  from  the  solu- 
tion, carefully  washed  in  water,  and  in  dilute  acetic  acid  (0.1  per  cent.)  if  the  solution 
used  was  alkaline,  again  washed  in  water,  transferred  to  alcohol,  stained  in  muchse- 
matein,  cleared  and  mounted  in  balsam.  In  this  way  the  steps  of  the  reaction,  if  any, 
could  be  accurately  followed.  I  found  that  the  contents  of  the  glands  of  Brunner 
placed  in  a  solution  of  barium  hydroxide  saturated  at  room  temperature  disappeared 
in  two  hours  ;  that  of  the  pyloric  gland  cells,  of  the  gastric  epithelial  cells,  and  of  the 
goblet  cells  required  ten  to  twenty-four  hours  for  complete  solution.  The  granules  of 
the  Paneth  cells  were  unaffected.  The  mucin  from  all  the  above  cells  was  unaffected 
by  treatment  with  5  per  cent,  solution  of  hydrochloric  acid  for  twenty-four  hours  at 
37°  C.  or  by  peptic  digestion  for  the  same  length  of  time.  The  difference  in  the  solu- 
bility of  the  mucin  from  the  several  sources — Brunner's  cells,  gastric  epithelium, 
goblet  cells,  etc. — may  be  due  to  the  unequal  action  of  the  fixing  fluid  (alcohol  bichro- 
mate sublimate),  but,  on  the  other  hand,  may  indicate  a  chemical  difference  in  the 
nature  of  the  mucins  from  these  several  sources. 

The  cells  of  the  pyloric  glands  in  the  opossum  resemble  the  cells  of  the  glands  of 
Brunner  very  closely.  The  differences  which  may  be  observed  are  of  secondary 
importance.  The  tubules  of  the  pyloric  glands  and  the  cells  composing  them  are  dis- 
tinctly smaller  than  those  of  the  glands  of  Brunner.  The  internal  structure  of  the 
cells  is,  however,  almost  identical.  The  most  obvious  differences  between  the  pyloric 
glands  and  the  glands  of  Brunner  consist  in  the  great  number  of  cells  of  StOhr  visible 
in  the  former  and  in  the  greater  ease  with  which  the  contained  secretion  may  be  stained 
with  muchsematein.  The  mucin  of  the  pyloric  glands  may  be  stained  by  a  weaker 
solution  of  muchaematein,  in  which  the  glands  of  Brunner  remain  colorless. 

III.  THE  GLANDS  OF  BRUNNER  OP  THE  CARNIVORA 

Next  to  the  opossum  in  order  of  simplicity,  as  regards  the  structure  of  the  glands 
of  Brunner  and  their  relation  to  the  pyloric  glands,  come  the  genera  of  the  placental 
orders,  Carnivora  and  Insectivora.  The  structure  and  extent  of  the  glands  of  Brunuer 
in  the  cat  and  dog  have  been  the  subjects  of  numerous  researches  and  are  well  known. 
The  facts  as  they  present  themselves  in  these  animals  are  the  foundations  for  most  of 
our  knowledge,  both  physiological  and  histological,  concerning  the  glands  of 
Brunner. 

From  the  standpoint  of  specialization,  the  glands  of  Brunuer  of  the  cat  and  dog 
present  an  advance  on  the  condition  fouud  in  the  opossum,  inasmuch  as  the  ducts, 

292 


ROBERT  RUSSELL  BENSLEY  17 

instead  of  opening  in  groups  on  a  special  area  of  the  mucous  membrane  from  which 
glands  of  Lieberkuhn  and  villi  are  absent,  penetrate  between  the  former,  traverse  the 
whole  thickness  of  the  mucous  membrane,  and  open  independently,  on  the  surface,  between 
the  bases  of  the  intestinal  villi.  The  epithelium  at  the  mouth  of  these  ducts  presents,  as 
Schiefferdeoker  (1884)  has  pointed  out,  a  quite  remarkable  resemblance  to  gastric 
epithelium,  the  same  differences,  however,  being  recognizable,  as  have  been  already 
described  for  the  epithelium  of  the  defects  of  the  Brunnerian  area  of  the  opossum. 

The  resemblance  of  the  cells  of  the  glands  of  Brunner  of  these  animals  to  those  of 
the  pyloric  glands  is  a  very  close  one — so  close,  indeed,  that  one  is  justified  in  declar- 
ing that  they  are  identical.  In  the  glands  of  Brunner  of  the  cat  the  subdivision  of  the 
secretion  into  two  masses  is  very  obvious  ;  in  the  dog,  in  the  resting  condition,  the  cell 
is  so  filled  with  secretion  that  such  a  subdivision  cannot  be  made  out,  but  if  the  cells 
be  exhausted  by  stimulation  with  pilocarpine  or  by  feeding,  it  is  seen  that  new  secre- 
tion is  deposited  in  the  neighborhood  of  the  nucleus  and  forms  a  proximal  mass.  The 
essentially  similar  changes  in  the  pyloric-gland  cells  under  experimental  conditions  of 
secretion  have  already  been  described  by  the  writer  (1898).  The  differences  between 
the  pyloric  and  Brunner's  glands  of  these  animals  consist  in  the  greater  size  of  the 
constituent  tubules,  to  a  large  extent  due  to  the  expansion  of  the  lumen,  and  in  the 
absence  of  the  granular  cells  of  Stehr  from  the  glands  of  Brunner.  Another  difference 
which  is  particularly  obvious  in  the  cat  is  the  greater  variability  of  the  cells  of  Brunner's 
glands  in  respect  to  the  amount  of  mucin  they  contain. 

In  both  of  these  animals  the  secretion  stains  readily  with  muchaematein  and 
mucicarmiiie,  applied  in  the  way  described  above.  For  the  cat  and  dog,  however,  I 
have  obtained  the  most  satisfactory  stain  by  employing  the  eosin-aurantia-indulin  mix- 
ture of  Ehrlich  diluted  with  twenty  times  its  volume  of  water.  By  this  means  the 
secretion  of  the  glands  of  Brunner  and  of  the  pyloric  glands  is  stained  intensely  blue, 
the  rest  of  the  tissue  red  or  yellow.  The  indulin  mixture  discriminates  between  the 
mucin  of  the  glands  of  Brunner  and  that  of  the  goblet  cells  and  of  the  gastric  epithe- 
lium, and  brings  out  exquisitely  the  transition  in  type  of  the  epithelium  in  passing  up 
the  ducts. 

In  the  raccoon,  the  glands  of  Brunner  extend  a  distance  of  about  35  mm.  into  the 
duodenum.  They  form  an  aggregate  of  a  number  of  fairly  distinct  elliptical  lobules 
imbedded  in  a  tela  submucosa  composed  of  unusually  dense,  close-textured,  collagenic 
fibrous  tissue.  The  lobules  are  confined  to  the  tela  submucosa  except  for  the  short 
distance  (1.6mm.)  at  the  beginning  of  the  intestine  where  a  few  groups  of  Brunner's 
glands  (pyloric  glands?)  occur  in  the  deeper  layers  of  the  mucosa  among  the  some- 
what dispersed  fibers  of  the  lamina  muscularis  mucosae. 

The  lamina  muscularis  mucosse  is  continuous,  but  perforated  here  and  there  by 
the  ducts  of  the  glands  of  Brunner.  For  some  distance  on  each  side  of  the  sphincter 
pylori  it  is  composed  of  longitudinal  fibers  only,  the  circular  inner  layer  making  its 
appearance  toward  the  end  of  the  glands  of  Brunner.  From  the  outer  surface  of  the 

293 


18          THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNER 

lamina  muscularis  mucosse  smooth  muscular  fibers  radiate  into  the  connective  tissue  of 
the  tela  submucosa,  forming  a  more  or  less  perfect  network  around  the  glandular  lobules. 
In  the  mucous  membrane  the  intestinal  epithelium  and  glands  begin  just  beyond  the 
pyloric  sphincter,  there  being  as  a  rule  very  little  intermingling  of  intestinal  and  gas- 
tric elements,  although  for  a  short  distance  ( 8  mm. )  a  few  pyloric  glands,  serving  as 
ducts  for  the  superficial  glands  of  Brunner,  could  be  discerned. 

The  lobules  are  composed  of  branching  tubules  of  large  diameter  and  lined  by 
large  secretion- filled  epithelial  cells.  Each  lobule  is  provided  with  a  duct,  often  of 
extraordinary  size,  which  penetrates  the  lamina  muscularis  mucosse,  often  presenting 
at  this  point  an  ampulla-like  dilatation,  extends  through  the  mucous  membrane  a  vari- 
able distance,  and  terminates  in  a  shorter  or  longer  gland  of  Lieberkuhn.  Rarely 
these  ducts  reach  the  free  surface  without  being  intercepted  by  a  gland  of  Lieberkuhn. 
A  minority  of  the  ducts  open  into  the  bottoms  of  the  intestinal  glands,  directly  after 
having  passed  through  the  lamina  muscularis  mucosaB.  The  majority  extend  about 
half  the  thickness  of  the  mucous  membrane,  become  abruptly  reduced  in  size,  and  are 
continued  to  the  surface  by  a  gland  of  Lieberkuhn.  A  few  reach  the  surface  without 
alteration  in  the  type  of  epithelial  cells.  Whenever  the  ducts  open  into  a  gland  of 
Lieberkuhn,  the  change  of  epithelium  is  abrupt. 

The  cells  of  the  glands  of  Brunner  from  the  single  individual  available  for  exami- 
nation resembled  the  secretion-filled  stage  of  the  opossum's  glands.  They  were  from 
16  M  to  22 /*  in  height  and  filled  with  secretion.  In  iron  hsematoxylin  preparations  the 
cell  exhibited  a  delicate  network  with  very  large  meshes,  the  nucleus  being  crowded 
off  into  one  of  the  basal  angles  of  the  cell.  A  peculiarity  of  the  nuclei  in  these  cells 
was  that,  instead  of  occupying  the  middle  of  the  base  of  the  cells,  they  were  in  one 
corner  and  flattened  parallel  to  the  lateral  walls  of  the  cells.  Otherwise  the  condition 
was  the  same  as  in  other  secretion-filled  mucous  cells.  In  strong  muchcematein  solu- 
tions the  cells  stained  intensely  and  showed  a  very  coarse  network  of  blue-stained 
trabeculce. 

No  trace  of  a  division  of  the  secretion  into  two  masses  was  discernible  in  the 
cells  of  the  gland  tubules,  but  those  of  the  ducts  exhibited  a  distinct  transverse  band 
of  cytoplasm,  so  dividing  the  secretion. 

The  resemblance  between  the  cells  of  the  glands  of  Brunner  and  those  of  the 
pyloric  glands  in  the  raccoon  is  very  close,  the  only  character  in  which  a  difference 
could  be  made  out  being  the  subdivision  of  the  secretion  into  two  masses,  which  was 
obvious  in  the  pyloric  glands,  but  in  the  glands  of  Brunner  visible  only  in  the  cells  of 
the  ducts. 

In  the  mink  (Lutreola  vison),  the  glands  of  Brunner  are  confined  to  the  submu- 
cosa and  form  a  compact  mass,  beginning  opposite  the  pyloric  sphincter  about  1  mm. 
beyond  the  point  of  greatest  thickness  of  the  latter,  and  extending  a  distance  of  about 
12  mm.  into  the  duodenum.  The  glands  are  composed  of  more  or  less  rounded  lobules 
closely  packed  together  in  the  submucosa1,  which  they  almost  fill  from  the  lamina 

294 


ROBERT  RUSSELL  BENSLEY  19 

musculnris  mucosse  to  the  tunica  muscularis.  The  amount  of  interlobular  connective 
tissue  is  relatively  small.  The  zone  begins  with  a  number  of  small  scattered  elliptical 
lobules  confined  to  the  superficial  portion  of  the  tela  submucosa,  but  rapidly  increases 
in  width  and  in  number  of  lobules  as  the  duodenum  is  descended.  The  greatest  width, 
0.7  mm.,  is  reached  at  a  distance  of  about  5.3mm.  from  the  beginning  of  the  zone. 
From  this  point  onward  the  layer  of  glands  gradually  diminishes  in  thickness  until  it 
disappears,  so  that  the  whole  mass  has  a  fusiform  shape  in  longitudinal  section. 

The  lamina  muscularis  rnucosae  is  continuous  throughout  except  at  the  points 
where  the  ducts  pass  through  to  enter  the  tunica  mucosa.  It  consists  of  a  thin  internal 
layer  of  circular  fibers  and  a  thicker  external  layer  of  smooth  muscle  fibers.  The 
structure  of  the  mucous  membrane  covering  the  Brunner's  glands  of  the  mink  is 
unique,  inasmuch  as  the  tunica  mucosa  of  the  proximal  half  of  this  region,  although 
on  the  duodenal  side  of  the  pyloric  sphincter,  is  covered  by  gastric  epithelium  and 
occupied  exclusively  by  glandulse  pyloricse  identical  in  structure  with  those  which 
occur  in  the  stomach  itself.  These  pyloric  glands  extend  into  the  duodenum  a  total 
distance  of  8.8mm.  (measured  from  the  summit  of  the  sphincter),  slightly  beyond  the 
point  of  greatest  thickness  of  the  glands  of  Brunner.  Here  they  are  abruptly  suc- 
ceeded by  the  intestinal  epithelium  and  glands. 

Beyond  the  point  where  this  change  takes  place,  however,  for  a  distance  of 
0.3mm.  one  may  meet  pyloric  glands  mingled  with  the  glands  of  Lieberktlhn,  opening 
into  typical  foveolse  gastricse,  and  may  even  find  patches  of  gastric  epithelium  on  the 
surface.  There  is  no  lymphatic  nodule  at  the  junction  of  gastric  and  intestinal 
mucosse;  both  of  these  mucosce  in  this  animal  are  singularly  poor  in  lymphatic  tissue. 

The  glands  of  Brunner  of  the  proximal  half  of  the  zone  open  directly  into 
branches  of  the  pyloric  glands  by  ducts  which  pierce  the  lamina  muscularis  mucosse. 
Beyond  the  point  where  the  intestinal  glands  of  Lieberkuhn  make  their  appearance 
the  glands  of  Brunner  open  either  into  the  glands  of  Lieberkuhn  or  into  the  pyloric 
glands  with  which  these  are  mingled.  In  the  distal  parts  of  the  area  independent 
ducts  are  rare,  the  glands  opening  almost  exclusively  into  the  bottoms  of  Lieberkuh- 
nian  glands.  A  curious  fact  in  these  latter  instances  is  that  the  epithelium  of  the 
proximal  branches  in  the  lobule  may  be  lined  by  cylindrical  and  goblet  cells ;  in  other 
words,  the  glands  of  Lieberkuhn,  instead  of  receiving  the  ducts  of  the  glands  of 
Brunner  in  the  tunica  mucosa  internal  to  the  lamina  muscularis  mucosse,  perforate  the 
latter  and  may  subdivide  into  several  branches  which  retain  the  typical  epithelium 
before  receiving  the  tubules  formed  of  the  epithelium  characteristic  of  the  glands  of 
Brunner.  We  may  thus  have  illustrated  in  this  single  animal  all  the  various  kinds  of 
ducts  between  two  extremes,  one  of  these  being  the  condition  in  which  independent 
d"ucts  lined  by  glandular  epithelium  and  opening  into  gastric  foveolse  are  present ;  the 
other,  that  in  which  the  branched  glands  of  Lieberkuhn  penetrate  the  tela  submucosa 
and  receive  the  tubules  of  Brunner's  glands. 

The  tubules  of  the  glands  of  Brunner  in  the  mink  bear  a  very  close  resemblance 

295 


20          THE  STRUCTURE  OF  THE  GLANDS  OP  BRUNNER 

to  those  of  the  cat.  They  have,  as  a  rule,  a  rather  large  lumen  surrounded  by  secret- 
ing cells.  The  average  size  of  the  tubules  is  about  40  /*,  but  some  are  as  much  as  77  /* 
in  width. 

The  cells  vary  in  width  from  11  /t  to  15  p,  the  two  extremes  being  often  found  on 
opposite  sides  of  the  same  tubule.  The  cells  correspond  very  closely  in  structure  to 
those  of  the  opossum  ;  indeed,  Fig.  2  would  illustrate  equally  well  a  typical  tubule 
from  the  mink.  In  each  cell  two  well-defined  secretion  masses  may  be  discerned 
separated  by  a  transverse  band  of  cytoplasm.  The  secretion  in  these  cells  stains 
strongly  in  muchcematein  applied  as  indicated  above.  The  amount  of  secretion 
contained  in  the  cells,  and  so  the  amount  of  cytoplasm,  vary  respectively,  in  the 
material  examined,  with  the  distance  from  the  sphincter  pylori.  In  the  glands 
near  the  sphincter,  the  cells  contain  a  large  amount  of  basal  cytoplasm  and  a 
spherical  nucleus.  The  proximal  mass  of  secretion  is  small  and  stains  less  intensely 
in  muchsematein.  Going  down  the  zone,  the  size  of  the  proximal  mass  progressively 
increases  and  encroaches  on  the  basal  cytoplasm,  the  nucleus  at  the  same  time  becom- 
ing correspondingly  compressed  and  crescentic  and  crowded  to  the  extreme  base  of 
the  cell. 

If  we  compare  the  cells  of  the  glands  of  Brunner  of  the  proximal  part  of  the  zone 
with  the  cells  of  the  pyloric  glands  which  immediately  overlie  them,  there  appears  to 
be  an  almost  perfect  similarity  of  structure.  But  if  we  compare  Brunner's  gland  cells 
from  the  duodenal  end  of  the  zone  with  pyloric  glands  several  millimeters  above  the 
pyloric  sphincter,  some  differences  of  structure  are  apparent.  In  the  latter  instance 
the  tubules  and  cells  are  of  about  the  same  size,  but  in  the  pyloric  glands  the  cells  are 
to  a  large  extent  filled  with  cytoplasm.  The  proximal  mass  of  secretion  in  these 
upper  pyloric-gland  cells  is  scarcely  visible,  and  the  distal  mass  next  to  the  lumen 
occupies  often  less  than  one-fifth  of  the  whole  length  of  the  cell.  The  nuclei  are 
spherical.  Again  in  the  pyloric  glands  as  the  sphincter  is  approached  the  amount  of 
secretion  in  the  gland  cells  is  gradually  increased.  There  is  thus  in  the  mink  the  most 
perfect  transition  between  the  pyloric  glands,  on  the  one  hand,  and  the  intestinal 
elements,  on  the  other. 

IV.  THE  GLANDS  OF  BRUNNER  OP  ERINACEUS 

In  the  European  hedgehog  the  glands  of  Brunner  form  a  mass  of  rather  large 
lobules,  beginning  at  the  pyloric  sphincter  and  extending  a  distance  of  9.3mm.  into  the 
duodenum.  The  greatest  thickness  of  the  mass  is  exhibited  at  the  beginning,  where 
the  lobules  fill  the  space  formed  by  the  sudden  falling  off  of  the  pyloric  sphincter. 
Here  it  reaches  a  thickness  of  1.8  mm.  From  this  point  it  gradually  diminishes  in 
thickness  to  the  end  of  the  zone. 

The  glands  are  separated  from  the  tunica  mucosa  by  a  lamina  muscularis  mucosaa 
composed  of  longitudinal  fibers,  which  form  a  continuous  layer  except  for  a  short  dis- 
tance just  at  the  beginning  of  the  duodenum,  where  the  fibers  are  somewhat  inter- 

296 


ROBERT  RUSSELL  BENSLEY  21 

rupted  by  the  ducts  of  the  proximal  lobules  of  the  glands  of  Brunner.  At  this  point 
the  pyloric  glands  and  the  glands  of  Brunner  appear  in  places  to  be  continuous.  The 
dispersed  fibers  of  the  lamina  muscularis  mucosse  radiate  out  among  the  lobules  of  the 
glands,  forming  a  partial  investment  for  them.  At  other  points  a  duct  which  is  pass- 
ing through  the  muscularis  mucosa?  may  give  off  a  few  gland  tubules  which  are  thus 
located  among  the  muscular  fibers  of  the  layer. 

The  ducts  of  the  glands  of  Brunner  in  the  hedgehog  are  independent  of  the 
glands  of  Lieberktlhn,  between  which  they  pass  to  open  on  the  free  surface.  A 
cluster  of  ducts  from  the  proximal  lobules  occurs  just  at  the  junction  of  the  intestinal 
and  the  gastric  mucous  membrane,  some  opening  between  the  gastric  epithelium  on 
one  side  and  the  first  villus  on  the  other ;  the  rest,  between  the  bases  of  the  first  short 
villi.  In  the  rest  of  the  zone,  the  ducts  occur  at  scattered  intervals  and  pass  through 
the  mucous  membrane  without  branching  or  showing  a  change  in  type  of  the  epithe- 
lium. The  glands  are  composed  of  richly  branching  tubules  radiating  from  a  central 
duct  in  each  lobule.  The  terminal  branches  are  frequently  short  acinus-like  tubules 
which  in  fixed  preparations,  however,  seldom  show  a  terminal  dilatation. 

The  tubules  are  composed  of  large  cells  of  rectangular  or  pyramidal  shape,  sur- 
rounding a  small  lumen.  The  latter  is  larger  in  the  tubules  which  are  nearer  the  main 
ducts  and  largest  in  the  ducts  themselves.  The  cells  in  the  specimen  from  which  the 
descriptions  are  taken  vary  in  length  from  16  n  to  21  /*,  the  average  being  18  M.  The 
cells  in  hsematoxylin  sections  are  clear,  transparent,  and  filled  with  secretion,  between 
the  droplets  of  which  a  delicate  network  may  be  made  out.  In  the  material  at  the 
writer's  disposal,  very  few  of  the  cells  of  the  gland  tubules  exhibit  a  subdivision  of 
the  secretion  into  two  masses.  The  nuclei  are  irregular  and  located  at  the  bases  of  the 
cells.  In  the  ducts,  on  the  other  hand,  the  amount  of  residual  protoplasm  gradually 
increases  as  the  surface  is  approached,  and  the  nucleus  expands  to  an  oval  shape  with 
the  long  axis  coinciding  with  that  of  the  cell.  In  the  stronger  mucha3matein  the  con- 
tained secretion  stains  deeply. 

The  cells  of  the  pyloric  glands  are  very  similar  to  those  of  the  glands  of  Brunner, 
although  they  are  somewhat  smaller  (average  length  15  /J-)  and  contain  less  mucin. 
Cells  of  Stohr  are  frequent  in  the  pyloric  glands,  but  absent  from  the  glands  of 
Brunner.  The  secretion  in  the  cells  of  the  pyloric  gland,  like  that  of  the  glands  of 
Brunner,  stains  with  stronger  muchaematein. 

V.  THE  GLANDS  OF  BRUNNER  OF  THE  RODENTIA 

Among  the  rodents  it  is  only  in  the  suborder  Myomorpha  that  the  glands  of 
Brunner  are  confined  to  the  proximal  section  of  the  duodenum,  between  the  pylorus 
and  the  opening  of  the  ductus  communis  choledochus.  In  the  rabbit,  belonging  to 
the  Duplicidentata,  the  American  porcupine,  belonging  to  the  Hystricomorpha,  and 
the  squirrel,  marmot,  and  gopher  (Oppel)  belonging  to  the  Sciuromorpha,  they  extend 
far  beyond  the  opening  of  the  bile  duct. 

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22          THE  STRUCTURE  OF  THE  GLANDS  OF  BBUNNEB 

In  the  rabbit,  according  to  Kuczynski  (1890),  these  glands  occur  in  the  duodenum 
OB  far  as  the  opening  of  the  ductus  paucreaticus,  a  distance  of  30  crn. 

The  glands  in  the  rabbit  make  their  appearance  in  the  tela  submucosa  at  the  point 
where  the  intestinal  epithelium  begins.  For  a  distance  of  about  three  and  one-half 
centimeters  they  form  two  groups,  one  located  in  the  tunica  niucosa,  the  other  in  the 
tela  submucosa.  These  groups  are  incompletely  separated  from  one  another  by  the 
lamina  muscularis  mucosse,  which  is  interrupted  here  and  there,  to  permit  of  commuui- 
cati'on  between  the  superficial  and  the  deep  glands,  and  the  passage  of  ducts  from  the 
latter  to  the  surface.  Throughout  the  rest  of  the  duodenum  the  glands  are  for  the 
most  part  confined  to  the  tela  submucosa,  although  here  and  there  a  duct  may  give  off 
a  small  group  of  branches  in  the  tunica  mucosa  before  reaching  the  submucous  group. 

The  ducts  of  the  superficial  lobules  of  the  glands  open  directly  into  the  glands  of 
Lieberkuhn;  those  belonging  to  the  submucous  group  preserve  their  characteristic 
epithelium  for  a  short  distance  after  passing  through  the  lamina  muscularis  mucosse, 
but  are  in  the  majority  of  cases  continued  to  the  free  surface  by  a  gland  of  Lieberkiilm. 
There  are,  however,  a  few  independent  ducts  in  which  the  epithelium  retains  the  type 
characteristic  of  the  glands  of  Brunner  as  far  as  the  free  surface. 

The  glands  of  Brunner  of  the  rabbit  are  unique  in  structure,  inasmuch  as  they 
contain  two  kinds  of  cells.  This  fact  was  discovered  by  Schwalbe  (1872)  who  described 
the  more  deeply  staining  elements  as  independent  glands,  having  the  same  structure 
as  the  pancreas.  _ 'Schwalbe' s  observations  have  been  confirmed  by  Dekhuyzen  (1888) 
and  Kuczynski  (1890).  The  latter  author  showed  that  the  deeply  staining  elements 
did  not,  as  Schwalbe  thought,  form  independent  glands,  but  occurred  along  with  the 
clear  cells  in  the  same  tubules.  Dekhuyzen  came  to  the  conclusion  that  the  two  kinds 
of  cells  represented  different  functional  stages  of  the  same  element,  and  claimed  to 
have  seen  intermediate  types.  Castellant  (1898)  gives  an  excellent  description  of  the 
deeply  staining  cells,  in  which  he  observed  the  small  refractive  granules  of  the  distal 
zone  and  the  striation  (basal  filaments)  of  the  basal  zone.  He  takes  exception  to  the 
conclusion  of  Dekhuyzen  on  the  grounds  that  he  could  not  discover  any  intermediate 
stages  between  the  two  kinds  of  cells,  and  that  deeply  staining  cells  are  altogether 
absent  in  the  glands  at  the  beginning  of  the  duodenum.  Castellant  does  not  come  to 
any  definite  conclusion  as  to  the  relative  specificity  of  the  two  kinds  of  cells,  but 
suggests  an  interesting  comparison  between  the  glands  of  Brunner  of  the  rabbit  and 
the  mixed  glands  of  the  trachea. 

My  own  observations  confirm  the  conclusion  of  Kuczynski  that  the  deeply  staining 
cells  occur  in  the  same  tubules  as  the  clear  cells.  The  glands  of  the  rabbit  are  of  the 
compound  acinotubular  type,  the  main  tubules  and  some  of  the  terminal  acini  being 
composed  of  clear  cells ;  many  of  the  terminal  tubules  or  acini,  of  deeply  staining  cells. 
The  deeply  staining  cells  may  occur  (contra  Castellant)  in  the  glands  of  Brunner  at 
the  very  beginning  of  the  duodenum. 

The  transparent  tubules  are  formed  by  large,  clear  cuboidal  cells  surrounding  a 

298 


ROBERT  RUSSELL  BENSLEY  23 

lumen  16 p  to  20 p  in  width.  The  clear  cells  of  the  glands  of  Brunner  of  the  rabbit 
are  mucous  cells,  very  similar  in  type  to  those  of  the  animals  already  described.  A 
number  of  tubules  formed  by  cells  of  this  type  is  represented  in  Plate  XXI,  Fig.  5. 
The  body  of  the  cell  presents  a  coarsely  reticular  structure,  the  meshes  of  which  are 
filled  with  the  reserve  secretion  of  the  cell.  This  secretion  may  be  stained  by  the  use 
of  the  stronger  muchEematein,  or  of  mucicarmine,  or  of  Mann's  methyl  blue-eosin  in 
which  it  stains  blue,  or  of  the  eosin-aurantia-indulin  mixture  recommended  by  the 
writer  for  staining  the  secretion  of  the  pyloric  glands.  The  appearance  of  the  secre- 
tion when  so  stained  differs  according  to  the  mode  of  fixation  and  subsequent  treatment 
of  the  tissue.  In  material  fixed  in  aqueous  solutions  of  corrosive  sublimate,  the  secre- 
tion presents  the  reticular  appearance  characteristic  of  mucous  cells.  The  same  remark 
is  true  of  material  fixed,  without  previous  removal  of  the  tunica  muscularis,  in  the 
alcoholic  sublimate-bichromate  mixture.  If,  however,  the  muscular  coat  of  the  intestine 
is  removed,  and  the  organ  then  fixed  in  the  last-mentioned  mixture,  so  as  to  permit  the 
sublimate  and  bichromate  to  come  at  once  into  contact  with  the  cells,  the  secretion  is 
found  to  be  in  the  form  of  distinct  granules  which  are,  when  so  fixed,  more  resistant  to 
the  action  of  water  and  therefore  more  permanent  in  preparations  than  the  correspond- 
ing structures  in  the  cells  of  the  opossum.  According  to  the  phase  of  functional 
activity  the  secretion  is  subdivided  more  or  less  completely  into  proximal  and  distal 
masses.  In  Fig.  5,  which  represents  the  fully  loaded  condition,  traces  of  the  transverse 
band  of  cytoplasm  separating  the  two  masses  are  still  visible  in  most  of  the  cells.  The 
basal  cytoplasm  is  small  in  amount  and  contains  no  basal  filaments. 

Sections  of  the  fresh  tubule  examined  in  blood  serum  or  in  salt  solution  appear 
perfectly  transparent,  the  granules  of  secretion  corresponding  so  closely  in  refractive 
index  to  the  surrounding  medium  that  they  remain  invisible. 

In  material  fixed  in  absolute  alcohol  and  tested  by  Macallum's  microchemical 
method  for  the  detection  of  organic  compounds  of  iron,  a  very  faint  positive  reaction  is 
obtained  in  the  cytoplasm  around  the  nucleus.  By  Macallum's  modification  of  Lilien- 
feld  and  Monti's  method  for  the  microchemical  detection  of  phosphorus,  the  cytoplasm 
gives  a  reaction  no  stronger  than  that  obtained  in  the  cytoplasm  of  the  cylindrical  cells 
of  the  surface  epithelium.  The  secretion  masses  remain  colorless  in  this  test. 

Both  in  the  fresh  tissue  and  in  stained  sections,  the  dark  tubules  present  appear- 
ances totally  different  from  those  just  described.  In  the  fresh  material  examined  in 
blood  serum  the  dark  tubules  exhibit  two  well-marked  zones.  The  outer  zone  is 
perfectly  clear  and  transparent,  no  structures  whatever  being  visible  in  it.  The  inner 
zone,  on  the  contrary,  is  occupied  by  large  numbers  of  closely  packed,  minute,  highly 
refractive  granules.  The  appearance  of  such  a  fresh  tubule  is  shown  in  Plate  XXI, 
Fig.  7.  The  resemblance  to  a  fresh  pancreatic  tubule  or  to  an  active  acinus  of  a 
serous  gland  is  striking. 

In  the  stained  preparations  these  tubules  are  distinguished  from  the  mucous 
tubules  by  their  remarkable  staining  capacity.  The  lumen  is  so  small  as  to  be  scarcely 

299 


24          THE  STRUCTURE  OP  THE  GLANDS  OF  BRUNNEB 

visible  in  many  tubules.  The  cells  are  of  about  the  same  height  as  the  mucous  cells, 
but  as  a  rule  narrower  and  more  triangular  in  outline. 

The  two  zones  visible  in  the  living  cell  are  even  more  obvious  in  the  stained 
preparations.  The  basal  clear  zone  of  the  living  cell  is  distinguished  by  its  great 
capacity  for  staining.  In  hsematoxylin,  carmine,  toluidin  blue,  safranin,  and  many 
other  nuclear  dyes,  the  basal  zone  of  the  cell  stains  intensely.  The  substance  on  which 
this  capacity  for  staining  depends  is  not  evenly  distributed  in  the  basal  zone,  but,  as 
Castellant  (1898)  has  pointed  out,  gives  to  the  zone  an  indistinct  radially  striated 
appearance  (Plate  XXI,  Fig.  6). 

The  inner  zone  of  the  cell,  unless  special  precautions  have  been  taken  to  preserve 
and  stain  the  granules,  appears  clear  with  a  fine  alveolar  structure,  the  spaces  corre- 
sponding to  the  granules  of  the  fresh  cell,  the  framework  to  the  cytoplasm  separating 
them. 

By  Macallum's  microchemical  test  for  organic  iron,  a  very  intense  positive  reaction 
is  obtained  in  the  deeply  staining  substance  of  the  basal  or  proximal  zone.  A  similarly 
intense  reaction  is  obtained  in  this  substance,  after  extraction  of  the  lecithin  by  alcohol 
and  ether  in  a  Soxhlet  apparatus,  by  the  use  of  Macallum's  microchemical  reaction  for 
the  detection  of  organic  phosphorus.  By  the  latter  method  a  positive  result  also  is 
obtained  in  the  granules  of  the  inner  distal  zone. 

The  microchemical  reactions  indicate  that  the  substance  of  the  basal  zone  on 
which  the  capacity  for  basic  dyes  depends  is  a  nucleo-albuniin  or  nucleoproteicl  sub- 
stance, probably  the  latter,  similar  to  that  found  in  the  basal  zones  of  cells  from 
various  serous  glands,  as,  for  example,  the  pancreas,  the  chief  cell  of  the  body  of  the 
gastric  gland,  and  the  cells  of  the  serous  glands  of  the  gustatory  area  of  the  tongue, 
the  serous  cells  of  the  human  submaxillary,  etc.  For  this  substance,  the  writer  has 
employed  the  term  "  prozymogen,"  first  used  by  Macallum  (1891),  to  designate  a  sub- 
stance which  he  found  in  the  pancreatic  cell  by  the  use  of  safranin.  He  afterward 
(1895)  employed  the  name  to  designate  the  iron-holding  organic  compound  of  the 
basal  zone  of  the  pancreatic  cell,  which  he  identified  with  the  safraninophilous  sub- 
stance of  his  earlier  studies.  In  1895  Mouret  described  the  reciprocal  relation 
between  the  deeply  staining  filaments  of  the  pancreatic  cell  previously  described  by 
Eberth  and  Mflller  (1892),  Platner  (1889),  Macallum  (1891),  and  others,  and  the 
zymogen  granules,  and  applied  independently  of  Macallum  and  without  being  aware 
of  his  work,  the  name  "prezymogen"  to  the  substance  of  the  basal  zone.  In  1896 
Solger  described,  without  attempting  an  interpretation  of  them,  the  deeply  staining 
filaments  in  the  basal  zone  of  the  serous  cells  of  the  human  submaxillary  gland,  and 
Erik  Muller  (1895)  observed  similar  structures  in  the  submaxillary  gland  of  the 
guinea  pig.  In  the  same  year  I  (1896)  published  a  preliminary  account  of  my 
researches  on  the  gastric  glands  of  vertebrates,  in  which  it  was  shown  by  micro- 
chemical  tests  that  the  so-called  basal  filaments  of  serous  cells  owed  their  affinity  for 
basic  dyes  to  the  fact  that  they  contained  a  chemical  substance  "similar  to  chroinatin 

300 


ROBERT  RUSSELL  BENSLEY  25 

which  was  identified  as  Macallum's  prozymogen.  In  this  study  it  was  shown  that  the 
prozymogen  of  the  base  of  the  cell  increases  and  diminishes  in  amount  pari  passu 
with  the  diminution  and  increase  respectively  of  the  zymogen  granules,  and  it  was 
therefore  regarded  as  an  antecedent  substance  of  the  latter.  The  occurrence  of  similar 
substances  in  the  basal  zones  of  the  serous  cells  of  the  glands  of  von  Ebner  and  of  the 
oesophageal  glands  of  the  frog  was  also  described,  and  it  was  suggested  that  the  basal 
filaments  of  Solger  and  Erik  Mtiller  were  of  a  similar  nature. 

Since  the  publication  of  this  paper,  the  presence  of  so-called  basal  filaments  has 
been  demonstrated  in  a  host  of  serous  cells  from  various  sources  by  Zimmermann 
(1898),  Gamier  (1900),  Theohari  (1899),  Cade  (1901),  and  others.  The  three  last 
mentioned  accept  in  a  modified  form  the  interpretation  of  the  writer  that  the  so-called 
basal  filaments  contain  the  antecedent  substance  of  the  zymogen  granules — a  concep- 
tion which  was  also  adopted  by  Solger  (1899)  for  his  basal  filaments  of  the  sub- 
maxillary  gland  of  man. 

It  is  clear  from  the  foregoing  that  the  dark-staining  cells  of  the  rabbit's  glands 
of  Brunner  agree  with  serous  cells  of  many  other  glands  in  containing  large  quantities 
of  prozymogen  in  their  outer  zones  and  in  containing  in  their  inner  zones  granules, 
visible  on  the  fresh  cell,  of  a  phosphorus-holding  substance,  presumably  some  sort  of 
zymogen.  This  fact  should  speedily  lead  to  a  chemical  examination  of  the  glands  of 
Brunner  from  this  animal  to  determine  the  nature  of  the  secretion  of  these  cells.  On 
anatomical  and  microchemical  grounds,  there  would  appear  to  be  a  stronger  possibility 
of  a  positive  result  in  the  search  for  important  digestive  ferments  in  the  glands  of 
Brunner  of  this  animal  than  in  those  of  any  other  mammal. 

The  conclusion  that  the  dark  cells  of  the  glands  of  Brunner  of  the  rabbit  are 
serous  cells  is  further  borne  out  by  the  negative  evidence  afforded  by  staining  in 
muchaematein  and  mucicarmine,  in  which  the  secretion  granules  of  these  cells  remain 
absolutely  colorless. 

The  facts  in  connection  with  the  glands  of  Brunner  of  the  rabbit  may  be  summed 
up  as  follows :  The  glands  of  Brunner  of  the  rabbit  are  mixed  glands  (well  compared 
by  Castellant  to  the  mixed  glands  of  the  trachea)  composed  of  mucous  portions,  the 
cells  of  which  stain  strongly  in  muchaematein,  mucicarmine,  etc. ;  and  serous  portions, 
which  do  not  stain  in  these  solutions,  but  on  the  contrary  possess  a  basal  zone  with 
indistinct  radial  striation  containing  a  large  amount  of  prozymogen,  which  may  be 
demonstrated  by  the  microchemical  reactions  for  iron  and  phosphorus,  and  an  apical 
zone  in  which  minute  granules,  presumably  of  zymogen,  are  to  be  seen.  These  two 
types  of  cell  are  morphologically  and  chemically  distinct  from  one  another,  and  no 
intermediate  types  are  to  be  found. 

The  pyloric  glands  of  the  rabbit  are  very  similar  to  those  of  the  glands  of 
Brunner,  but  the  former,  as  Dekhuyzen  (1888)  pointed  out,  are,  as  a  rule,  smaller  and 
contain  more  cytoplasm  and  less  secretion  than  the  latter.  However,  by  selecting  an 
animal  that  has  been  fasting  for  some  time,  pyloric  glands  may  be  obtained  the  cells  of 

301 


26          THE  STRUCTURE  OP  THE  GLANDS  OF  BBUNNEB 

which  are  indistinguishable  by  cytological  characters  from  those  of  the  glands  of 
Brunner.  In  the  pyloric  glands  many  cells  of  Stohr  may  be  seen.  In  the  glands  of 
Brunner  I  have  failed  to  find  any  of  these  elements. 

In  the  American  porcupine  the  duodenum  presents  at  its  beginning  a  flask- 
shaped  dilatation  about  3  cm.  in  length,  into  which  the  common  bile  duct  opens.  The 
glands  of  Brunner  are  not,  however,  confined  to  this,  but  extend,  as  in  the  rabbit,  for 
a  considerable  distance  into  the  duodenum.  The  piece  of  duodenum  available  for  this 
examination  was  12  cm.  in  length  and  throughout  contained  glands  of  Brunner.  In 
no  part  of  this  area  do  the  glands  reach  any  considerable  development.  They  form  a 
relatively  thin  layer  in  the  superficial  portion  of  the  submucosa,  composed  of  rather 
small  lobules  often  consisting  of  a  few  tubules  only.  Some  tubules  may  also  be  seen 
in  the  tunica  mucosa  above  the  lamina  muscularis  mucosse.  The  glands  begin 
immediately  distal  to  the  pyloric  sphincter.  At  this  point  a  well-defined  group  is 
present  in  the  mucosa  and  forms  the  direct  continuation  of  the  pyloric  glands  of  the 
stomach,  although  they  open  either  directly,  or  by  means  of  a  gland  of  Lieberktthn 
between  the  villi.  Separating  these  from  the  small  lobules  in  the  submucosa  there  is 
a  well-defined  lamina  muscularis  mucosse  composed  of  a  thick  outer  longitudinal 
stratum  and  a  thin  incomplete  inner  circular  layer.  In  the  rest  of  the  region  the 
lamina  muscularis  mucosae  is  thin,  composed  almost  wholly  of  longitudinal  fibers  and 
much  interrupted  by  the  passage  of  ducts.  The  ducts  of  the  glands  of  Brunner  after 
passing  through  the  lamina  muscularis  mucosaa  open  either  directly  into  the  bottoms 
of  the  glands  of  Lieberkuhn  or  ascend  as  independent  ducts  for  a  short  distance  and 
open  into  the  sides  of  the  glands  of  Lieberkuhn  shortly'  before  reaching  the  surface. 
In  the  latter  case  the  duct  is  usually  joined  by  a  number  of  tubules  which  are  located 
in  the  mucosa.  There  are  also  in  the  mucosa  small  groups  of  Brunner' s  glands  which 
open  independently  into  the  sides  or  bottoms  of  the  glands  of  Lieberkuhn  without 
being  connected  with  those  located  in  the  submucosa  or  with  their  ducts. 

The  glandular  tubules  are  formed  of  cells  of  a  rectangular  shape  8  ^  to  17  M  in 
height,  the  average  being  about  13  /*.  The  cells  show  great  uniformity  in  structure, 
notwithstanding  differences  in  size.  The  nucleus  has  a  distinct  oxyphile  nucleolus,  is 
situated  at  the  base  of  the  cell,  and  is  oval  in  shape,  but  is  in  some  cases  somewhat 
flattened  or  irregular  from  compression.  The  body  of  the  cell  is  transparent  in  hamia- 
toxylin  preparations.  There  is  but  little  cytoplasm  at  the  base  of  the  cell,  but  the 
secretion  is,  as  in  most  other  mammals,  distinctly  divided  into  two  masses  by  a  bridge 
of  cytoplasm  similar  to  that  illustrated  for  the  opossum  in  Fig.  2.  The  proximal  mass 
also,  as  in  the  opossum,  exhibits  a  coarser  cytoplasmic  network  than  the  distal  mass. 
In  strong  muchaematein  a  coarse  network,  composed  of  deeply  blue-stained  trabeculse, 
is  seen. 

The  few  pyloric  glands  which  are  found  on  the  intestinal  side  of  the  summit  of  the 
pyloric  sphincter  are  exactly  similar  in  all  structural  details  to  the  glands  of  Brunner. 
On  the  gastric  side,  however,  marked  differences  are  visible  which  are  particularly 

302 


ROBERT  RUSSELL  BENSLEY  27 

apparent  in  sections  stained  in  muchaematein.  In  such  preparations  the  pyloric-gland 
cells  exhibit  a  very  narrow  blue-stained  margin  along  the  lumen.  The  proximal  mass 
of  secretion  in  the  neighborhood  of  the  nucleus  is  either  wholly  absent  or  only 
indicated.  In  the  iron  hsematoxylin  sections  the  rest  of  the  cell  is  found  to  be  filled 
with  cytoplasm  free  from  secretion.  The  nucleus  is  full,  spherical  or  oval  in  outline, 
rich  in  chromatin,  and  separated  by  a  distinct  interval  from  the  base  of  the  cell.  In 
size  the  cell  is  about  the  same  as  the  Brunner's  gland-cell.  The  pyloric  glands  of  the 
porcupine  contain  numerous  cells  of  StOhr. 

In  the  guinea  pig  (Cavia  cobaya)  the  glands  of  Brunner  are  feebly  developed, 
although  they  extend  a  considerable  distance  into  the  duodenum,  according  to 
Kuczynski  (1890)  10  cm.  Even  at  its  thickest  part,  near  the  sphincter  pylori,  the  layer 
may  be  not  more  than  0.25  mm.  in  thickness.  For  a  distance  of  about  7  mm.  it  forms 
a  fairly  continuous  layer  of  thin  lobules,  but  beyond  this  point  the  lobules  become 
very  small  and  occur  at  increasingly  greater  intervals.  Each  lobule  is  composed  of  a 
cluster  of  branching  tubules  connected  by  a  short  duct  with  the  bottom  of  a  gland  of 
Lieberkuhn. 

The  tubules  are  composed  of  cuboidal  to  cylindrical  or  prismatic  cells,  varying  in 
height  from  9.5  (i  in  the  small  flattened  tubules  of  the  distal  lobules  to  14  p  to  18  p  in 
the  proximal  lobules.  The  nuclei  of  these  cells  are  irregularly  crescentic  in  shape  and 
are  located  in  the  extreme  outer  ends  of  the  cells.  The  body  of  the  cell  exhibits  the 
usual  transparent  reticular  appearance  when  examined  in  preparations  stained  in  iron 
hsematoxylin.  There  is  usually  in  the  middle  of  the  cell  a  slight  condensation  of  the 
cytoplasm,  a  suggestion  of  the  subdivision  of  the  secretion  into  two  masses.  In  some 
of  the  cells,  particularly  in  those  of  the  ducts  near  the  points  where  they  are  about  to 
open  into  the  glands  of  Lieberkiihn,  and  in  those  forming  the  tubules  of  the  small 
distal  lobules,  a  very  obvious  band  of  this  condensed  cytoplasm  may  stretch  across  the 
cell.  In  the  latter  case  the  cytoplasmic  trabeculae  which  separate  the  granules  of  the 
proximal  mass  are  coarser  in  texture  and  form  smaller  meshes  than  those  of  the  distal 
zone.  These  facts  indicate  the  probability  that  the  mechanism  of  secretion  in  the 
glands  of  Brunner  of  the  guinea  pig  is  similar  to  that  in  the  corresponding  glands  of 
the  opossum  and  many  other  mammals. 

The  cells  of  the  pyloric  glands  immediately  adjacent  to  the  pylorus  are  exactly 
similar  to  those  of  the  glands  of  Brunner.  The  glands  more  remote  from  the  pylorus 
are  formed  of  wedge-shaped  cells  12.8/*  to  14. 3  p  in  height,  surrounding  an  extremely 
small  lumen.  The  nuclei  of  these  cells  are  spherical  or  oval  in  shape  and  located  in 
the  base  of  the  cell.  The  secretion,  which  stains  readily  in  stronger  muchaematein, 
occupies  a  considerable  portion  of  the  cell  inclosed  by  the  meshes  of  a  cytoplasmic 
reticulum.  In  many  cells,  however,  there  is  a  proximal  continuous  cytoplasmic  layer 
around  the  nucleus  in  which  may  be  seen  in  iron-hsematoxylin  preparations  large, 
coarse,  rounded  granules,  concerning  the  interpretation  of  which  the  writer  is  in  doubt. 
Perhaps  they  represent  an  antecedent  substance  of  the  mucin.  This  is  the  only 

303 


28          THE  STRUCTURE  OP  THE  GLANDS  OF  BRUNNER 

instance  in  which  the  writer  has  seen  in  the  pyloric  glands  of  mammals  large  granules 
which  are  unstainable  by  mucin  stains  and  which  might  be  confused  with  zymogen 
granules.  They  do  not  occur  in  the  apical  zone  of  the  cell  in  the  midst  of  the  mass 
of  secretion,  nor  may  they  be  seen  in  the  cells  of  the  glands  of  Brunner.  Similar  large 
granules  occur  in  the  mucous  cells  of  the  pyloric  glands  of  Plethodon  cnjthronoius. 

In  the  ground  hog  (Arctomys  monax)  the  glands  of  Brunner  are  direct  continua- 
tions of  the  pyloric  glands.  They  begin  at  the  summit  of  the  pyloric  sphincter  and 
extend  a  considerable  distance  into  the  intestine  —  in  one  specimen  throughout  the 
whole  piece,  9.5  cm.  in  length,  available  for  examination.  At  no  point  does  the 
glandular  layer  reach  any  considerable  thickness,  the  maximum,  measured  in  one  speci- 
men, being  0.3  mm.  At  the  beginning  of  the  intestine,  the  lamina  muscularis  mucosse 
is  absent  and  the  glands  located  in  the  tunica  mucosa  and  in  the  tola  submucosa 
respectively  form  a  continuous  mass.  Farther  down  the  lamina  muscularis  IUUCOSJB  is 
represented  by  an  interrupted  band  of  longitudinal  fibers  which  subdivides  the  glands 
of  Brunner  into  two  groups,  one  located  in  the  submucosa  tissue,  the  other  in  the 
mucous  membrane.  At  the  lower  end  of  the  piece  the  lobules  are  small,  few  and  scat- 
tered, and  are  entirely  confined  to  the  tela  submucosa. 

A  few  of  the  ducts  at  the  beginning  of  the  zone  reach  the  surface  between  the 
villi.  Most  of  them,  however,  and  all  of  those  of  the  distal  portion  of  the  zone,  are 
connected  with  the  surface  by  means  of  a  gland  of  Lieberkuhn. 

The  glands  are  formed  of  rather  large  tubules,  31  /*  to  61  fj.  in  width,  of  which  the 
lumen  forms  approximately  one-third.  The  tubules  branch  much  less  freely  than  in 
the  other  genera  already  described. 

The  tubules  are  formed  of  large,  transparent,  secretion-filled  cells  12.7  p  to  19.5  ^ 
in  length.  The  nuclei  of  these  cells  are  elliptical,  in  some  cells  crescentic,  in  outline, 
and  placed  transversely  in  the  proximal  ends  of  the  cells.  The  transparent  bodies  of 
the  cells  exhibit  a  coarse  meshed  reticulum  composed  of  cytoplasmic  trabeculae,  the 
meshes  of  which  are  filled  with  the  secretion.  The  latter  forms  a  single  continuous 
mass  in  each  cell,  but  the  similarity  in  secretory  mechanism  between  this  cell  and  the 
corresponding  cells  of  the  opossum  is  shown  by  the  differences  in  character  of  the 
cytoplasmic  trabeculse  of  the  proximal  and  distal  portions  of  the  cell.  In  the  proximal 
portion,  the  trabeculae  are  coarser,  with  smaller  meshes,  so  that  the  cell  when  stained 
by  a  strong  cytoplasmic  stain  exhibits  two  zones.  At  the  junction  of  these  two  zones 
there  is  .a  slight  concentration  of  the  cytoplasm,  probably  corresponding  to  the  trans- 
verse band  which  in  the  intermediate  stage  of  the  opossum's  cells  separates  the  two 
masses  of  secretion. 

In  the  ground  hog  the  cells  of  the  pyloric  glands  are  similar  to  those  of  the 
glands  of  Brunner.  The  secretion  of  both  stains  readily  in  the  stronger  muchse- 
matein  and  in  mucicarmine.  In  Mann's  methyl  blue-eosin  the  secretion  of  the  pyloric 
glands,  as  well  as  that  of  the  cells  of  the  independent  ducts  of  the  glands  of  Bruuner, 
stains  more  intensely  than  that  of  the  glands  of  Brunner. 

304 


ROBERT  RUSSELL  BENSLEY  29 

As  in  the  marmot,  so  in  the  squirrel  and  gopher  (Spermophilus  citillus)  do  the 
glands  of  Brunner,  according  to  Oppel  (1897)  extend  a  considerable  distance  beyond 
the  point  where  the  common  bile  duct  enters  the  duodenum. 

In  the  red  squirrel  (Sciurus  hudsonicus)  I  have  traced  the  glands  for  a  distance 
of  24.6mm.  from  the  pyloric  sphincter.  In  the  specimen  from  which  this  measure- 
ment was  taken  the  glands,  for  a  distance  of  8.3  mm.,  formed  a  compact  mass,  in  which 
separate  lobules  could  not  be  made  out,  completely  filling  the  tela  submucosa.  For  a 
further  distance  of  6.45  mm.  the  lobules  were  distinct,  each  lobule  corresponding  to 
a  group  of  ducts.  For  the  last  ten  millimeters  only  scattered  small  lobules  were 
found,  each  consisting  of  a  few  acini,  opening  into  the  bottom  of  a  gland  of  Lieber- 
kuhii. 

The  glands  of  Brunner  in  the  squirrel  make  their  appearance  at  the  point  oppo- 
site the  pyloric  sphincter  where  the  intestinal  epithelium  succeeds  the  gastric 
epithelium.  At  this  point  they  are  located  both  in  the  tunica  mucosa  and  the  tela 
submucosa,  the  former  group  being  a  direct  continuation  of  the  pyloric  glands.  The 
lamina  muscularis  mucosae  of  the  intestine  at  this  point  is  very  imperfect,  so  that  the 
lobules  of  the  two  groups  are  continuous,  the  fibers  of  the  muscular  lamina  being  dis- 
persed among  the  lobules  of  the  glands  of  Brunner.  Beyond  the  first  five  millimeters 
the  lobules  which  are  seen  in  the  tunica  mucosa  are  less  numerous  and  are  mainly 
ducts  which  have  subdivided  before  penetrating  into  the  submucosa. 

In  one  specimen  examined  by  the  writer,  comprising  10  mm.  of  the  duodenum, 
the  ducts  of  the  glands  of  Brunner  were  independent  of  the  glands  of  Lieberkuhn  and 
were  lined  throughout  by  cells  similar  to  those  of  the  glandular  tubules.  In  a  second 
specimen,  in  which  the  pyloric  glands  extended  a  distance  of  1  mm.  into  the  duo- 
denum, the  proximal  group  of  glands  of  Brunner  opened,  together  with  the  pyloric 
glands,  by  means  of  the  gastric  foveolae.  Beyond  the  point  where  the  first  gland  of 
Lieberkuhn  made  its  appearance  independent  ducts  were  rare,  the  ducts  opening  into 
the  glands  of  Lieberkuhn  either  as  soon  as  they  entered  the  tunica  mucosa,  or  at 
various  levels  between  that  point  and  the  middle  of  the  layer.  The  scattered  lobules 
of  the  lower  10  mm.  of  the  zone  opened  exclusively  into  the  bottoms  of  the  glands  of 
Lieberkuhn. 

The  cells  composing  the  glands  of  Brunner  in  the  squirrel  are  subcylindrical  in 
shape  and  from  15. 9  p  to  17.2/4  in  height.  The  large  spherical  or  elliptical  nucleus, 
placed  in  the  proximal  half  of  the  cell,  is  surrounded  by  a  considerable  basal  layer  of 
cytoplasm.  The  inner  half  of  the  cell  is  clear  and  coarsely  reticular.  The  subdivision 
of  this  distal  clear  segment  of  the  cell  into  two  secondary  clear  zones  by  a  band  of 
cytoplasm  stretching  across  the  cell  from  side  to  side  is  very  obvious  in  many  of  the 
cells  of  the  glands  of  Brunner  of  the  squirrel. 

The  secretion  in  the  glands  of  Brunner  is  very  easily  stained,  even  over-ripe  solu- 
tions of  hsematoxylin  giving  successful  results.  In  stronger  muchsematein  it  stains 
intensely,  and  in  such  preparations  presents  the  appearance  of  a  coarse-meshed  net- 

305 


30          THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNEB 

work.  In  such  rnuchsematein  preparations  the  relations  of  the  two  masses  of  secre- 
tion may  be  readily  studied.  In  some  of  the  cells  the  two  masses  may  be  quite  distinct ; 
in  others  there  is  a  deeply  staining  mass  on  the  free  border  of  the  cell,  another  in  the 
interior,  and  a  faintly  staining  neck  of  secretion  connecting  them.  Sometimes  the 
proximal  mass  is  subdivided  into  two  secondary  masses,  one  on  each  side  of  the 
nucleus.  In  all  cases  the  proximal  mass  of  secretion  is  closely  applied  to  the  surface 
of  the  nucleus. 

None  of  the  cells  in  my  material  was  so  filled  with  secretion  that  the  nucleus  was 
flattened  by  compression. 

The  cells  of  the  pyloric  glands  for  a  short  distance  (about  6  mm.)  above  the 
sphincter  are  exactly  like  the  glands  of  Brunner,  but  exhibit  a  progressive  transition 
to  the  type  of  gland  cell  which  is  characteristic  of  the  rest  of  the  pyloric  area.  In  the 
latter  the  cells  in  form  and  size,  as  well  as  in  the  position  and  shape  of  their  nuclei,  are 
very  similar  to  the  cells  of  the  glands  of  Brunner.  The  differences  between  the  cells 
from  the  two  sources  are  concerned  only  with  the  amount  of  secretion  in  the  cell.  In 
the  pyloric-gland  cells  the  basal  cytoplasm  extends  to  very  near  the  free  border.  The 
mass  of  secretion  along  the  free  border  (distal  mass)  is  much  narrower  than  in  the 
glands  of  Brunner.  The  proximal  mass  in  the  interior  of  the  cell  is  represented  by  a 
few  scattered  granules  or  is  absent  altogether.  The  same  differences  thus  occur 
between  the  glands  of  Brunner  and  the  pyloric  glands  of  the  stomach  as  have  been 
already  remarked  in  the  mink  and  the  porcupine. 

The  Myomorpha  are  represented  in  the  writer's  material  by  the  mouse,  white  rat, 
dormouse  (Muscardinus  avellanarius),  deer  mouse  (Peromyscus),  and  muskrat  (Fiber 
zibethicus).  All  of  these  are  distinguished  from  the  forms  already  discussed  in  this 
paper  by  the  specialized  condition  of  the  stomach.  This  specialization  is  carried  to 
the  highest  degree  in  the  muskrat  and  deer  mouse,  in  which  the  gastric  glands  have 
disappeared  from  the  whole  stomach  with  the  exception  of  a  circular  area  of  fundus 
glands  at  the  summit  of  the  curvatura  major,  the  pyloric  glands  being  represented  only 
by  a  very  narrow  zone,  in  Fiber  a  few  millimeters  in  width,  around  the  pyloric  orifice. 
In  Mus  the  specialization  is  not  so  great  as  in  Fiber  and  Peromyscus,  the  whole  right 
division  of  the  stomach  being  occupied  by  gastric  glands.  In  the  dormouse  the 
stomach  is  also  specialized,  but  as  the  specialization  is  of  a  different  kind,  the  com- 
parison with  the  other  genera  as  regards  its  degree  cannot  be  made.  In  the  dormouse 
this  specialization  consists  in  the  formation  of  a  bulb-like  dilatation  containing  fundus 
glands,  at  the  point  where  the  oesophagus  joins  the  stomach. 

In  all  these  genera  the  glands  of  Brunner  are  of  small  extent  and  present  obvious 
differences  from  the  pyloric  glands,  more  particularly  in  the  muskrat,  deer  mouse,  and 
dormouse. 

In  the  muskrat,  the  glands  begin  abruptly  on  the  distal  side  of  the  pyloric 
sphincter  as  a  thick  mass  completely  filling  the  tela  submucosa  of  the  intestine  and 
extending  into  the  submucosa  underneath  the  small  pyloric-gland  area;  most  of  which 

306 


ROBERT  RUSSELL  BENSLEY  81 

is  on  the  distal  side  of  the  thickest  portion  of  the  sphincter.  The  lamina  muscularis 
mucosse  is  not  present  as  a  distinct  layer  throughout  the  zone,  but  is  represented  by 
bands  of  smooth  muscle  running  in  various  directions  among  the  glands.  The  glands 
of  Brunner  are  so  closely  packed  in  the  submucosa  and  deeper  layers  of  the  mucosa 
that  there  is  very  little  division  into  distinct  lobules.  The  ducts  open  into  the  bottoms 
or  sides  of  the  glands  of  Lieberkuhn. 

The  glands  have  the  usual  shape  and  structure,  i.  e.,  are  composed  of  repeatedly 
branching  tubules  terminating  in  elongated  pear-shaped  acini  or  short  tubules.  The 
whole  system  of  ducts  and  branches  is  formed  of  similar  cells. 

A  transverse  section  of  a  tubule  of  a  Brunner's  gland  from  the  muskrat  is  shown, 
highly  magnified,  in  Plate  XXII,  Pig.  9.  The  large  lumen  is  surrounded  by  somewhat 
cylindrical  cells  13 /t  to  17  M  in  height,  filled  with  secretion.  The  secretion  is  more 
or  less  obviously  divided  into  a  narrow  distal  and  a  larger  proximal  mass  by  a  band  of 
cytoplasm.  The  nucleus  is  flattened  or  crescentic,  and  located  in  the  extreme  outer 
end  of  the  cell. 

In  Plate  XXII,  Fig.  10  are  shown  two  glands  from  the  pyloric  region  of  the 
stomach  drawn  at  the  same  magnification.  The  differences  between  this  figure  and  the 
preceding  one  are  so  apparent  that  they  scarcely  require  comment.  The  cell  of  the 
pyloric  gland  is  much  smaller,  measuring  10.5/4  to  11.3/4.  The  secretion  is  confined 
to  a  narrow  band  along  the  free  border,  and  the  rest  of  the  cell  is  occupied  by  reticular 
cytoplasm  containing  an  oval  nucleus  rich  in  chromatin.  Several  cells  of  Stohr  may 
be  seen. 

The  secretion  contained  in  the  cells  of  the  glands  of  Brunner  and  of  the  pyloric 
glands  stains  readily  in  strong  muchsematein  ;  that  of  the  glands  of  Brunner  staining 
the  deeper  color.  That  this  difference  in  the  intensity  of  the  staining  does  not  mean 
a  greater  concentration  of  the  mucin  in  the  two  cells  is  indicated  by  the  result  obtained 
in  sections  stained  with  Mann's  methyl  blue-eosin.  In  this  the  secretion  contained  in 
the  cells  of  the  pyloric  glands  stains  deep  blue,  that  of  the  glands  of  Brunner  pale  blue. 

In  the  deer  mouse  the  extent  of  the  glands  of  Brunner,  measured  in  one  specimen, 
was  2.6  mm.  The  cells  of  the  glands  differed  from  those  of  the  muskrat  in  the  specimen 
examined  in  that  the  proximal  mass  of  secretion  was  less  compact  than  the  distal  mass, 
and  the  segment  of  the  cell  in  which  it  was  located  contained  relatively  more  cytoplasm. 
There  was  in  addition  a  narrow  basal  layer  of  cytoplasm  containing  the  slightly  flat- 
tened oval  nucleus.  The  cells  of  the  pyloric  glands  differed  from  those  of  Brunner's 
glands  in  this  animal  in  much  the  same  way  as  in  the  muskrat.  The  pyloric-gland 
cells  were  very  small,  had  a  relatively  large  oval  nucleus,  and  contained  but  a  small 
amount  of  stored-up  secretion.  The  secretion  of  both  kinds  of  cells  stained  readily  in 
stronger  muchaematein. 

In  the  dormouse  examined  (Muscardinus  avellanarius)  the  glands  extended  a 
distance  of  3.5  mm.  into  the  intestine.  Throughout  this  region  the  lamina  muscularis 
mucosse  was  represented  only  by  scattered  fibers.  The  glands  formed  a  thin  continu- 

307 


3'2          THE  STBUCTUBE  OP  THE  GLANDS  OP  BKUNNEB 

ous  layer  in  the  submucosa,  except  at  the  end  of  the  zone,  where  the  glands  termi- 
nated as  scattered  small  lobules.     The  ducts  emptied  into  the  glands  of  Lieberkuhn. 

The  differences  between  the  cells  of  the  glands  of  Brunner  and  those  of  the 
pyloric  glands  were  greater  in  this  animal  than  in  any  other  mammal  examined.  The 
former  cells  were  large,  transparent,  15-17 /t  in  height,  completely  filled  with  secre- 
tion without  any  indication  of  subdivision  into  two  masses.  The  nucleus  was  crescentic 
and  placed  in  the  base  of  the  cell.  The  cells  of  the  pyloric  glands  were  small,  9  p  in 
height,  contained  very  little  secretion,  and  possessed  a  relatively  large  oval  nucleus. 
The  secretion  contained  in  both  kinds  of  cells  stained  readily  in  muchaeuiatein  and 
mucicarmine. 

In  the  white  rat  the  glands  of  Brunner  begin  abruptly  as  a  mass  of  considerable 
thickness  occupying  the  space  formed  by  the  sudden  falling  off  in  thickness  of  the 
muscular  coat  on  the  dorsal  side  of  the  sphincter  pylori.  According  to  Kuczynski 
(1890),  they  extend  into  the  duodenum  a  distance  of  4.2  to  9  mm.  In  one  specimen 
measured  by  the  writer  the  extent  was  5.5mm.  The  greatest  thickness  of  the  mass 
is  exhibited  at  the  very  beginning  of  the  zone,  where  they  reach  a  thickness  of  1  mm. 
From  this  point  onward  the  zone  rapidly  diminishes  in  thickness  and,  beyond  a  point 
3mm.  to  3.5mm.  from  the  sphincter,  is  only  represented  by  scattered  small  lobules. 
Throughout  the  zone  the  lamina  muscularis  mucosse  is  defective.  The  glands  discharge 
into  the  glands  of  Lieberkuhn. 

The  cells  of  the  glands  of  Brunner  of  the  rat  have  recently  been  the  subject  of  a 
careful  study  by  Castellant.  This  author  finds  that  the  glands  of  Brunner  of  the  rat 
present  no  anatomical  relation  to  the  pyloric  glands  and  that  the  study  of  their  fine 
structure  places  them  still  farther  apart.  He  describes  the  cells  as  follows:  "Leurs 
cellules  secretantes,  de  forme  pyramidale  presentent  un  contenu  divise  en  deux  zones; 
IHine  basale,  granuleuse,  ou  se  trouve  le  noyau ;  1'autre,  apicale  qui  reste  claire,  quelque 
soit  le  liquide  fixateur  employe^  alcool,  liquide  de  Flemming,  acide  osmique."  He  found 
that  staining  with  hsematoxylin  after  Flemming's  fluid  did  not  color  the  clear  zone  of 
the  glands  of  Brunner.  Mayer's  mucicarmine  also,  in  Castellant's  hands,  gave  negative 
results,  but  thionin  staining  after  treatment  with  acetic  acid  gave  a  faint  reddish  color 
which  he  thought  might  be  interpreted  as  revealing  the  presence  of  a  little  rnucin. 

Castellant  also  studied  the  mechanism  of  secretion  in  the  cells  of  the  glands  of 
Brunner  of  the  rat  in  preparations  fixed  in  Flemming's  fluid.  He  found  that  for  the 
first  two  hours  of  digestion  these  cells  increase  in  size,  the  apical  clear  zone  increases 
in  size,  and  the  basal  granular  zone  is  diminished  in  amount.  From  the  third  hour  of 
digestion  onward  he  found  a  progressive  reduction  in  the  amount  of  secretion  in  the 
cell  to  the  end  of  the  seventh  hour,  when  the  cell  is  almost  wholly  granular  and  con- 
tains little  secretion. 

Castellant  does  not  specify  the  exact  nature  of  the  differences  which  he  found 
between  the  pyloric  gland  cells  and  those  of  Bruuner's  glands,  but  it  may  be  inferred  that 
the  clear  subdivision  of  the  cell  into  two  zones  in  the  glands  of  Brunner  is  one  of  them. 

308 


ROBERT  RUSSELL  BENSLET  33 

The  use  of  stronger  muchsematein  which  stains  intensely  the  secretion  of  the  cells 
both  of  the  glands  of  Brvmner  and  of  the  pyloric  glands  of  the  rat  has  enabled  me  to 
extend  somewhat  the  description  given  by  Castellant.  As  the  latter  points  out,  the 
distal  (apical)  zone  of  the  cell  in  the  rat  is  remarkable  for  the  extreme  tenuity  of  the 
fibers  of  the  cytoplasmic  network  which  it  contains.  It  does  not,  however,  contain  the 
whole  of  the  secretion  of  the  cell.  In  sections  stained  in  muchsematein  it  may  be  seen 
that  even  cells  in  the  resting  condition,  in  which  a  large  proximal  mass  of  cytoplasm 
is  visible,  may  contain  small  granules  of  stainable  secretion,  in  the  portion  of  this 
cytoplasm  between  the  nucleus  and  the  deeply  stained  secretion-filled  distal  zone  of  the 
cell.  In  some  of  the  cells  these  granules  have  so  increased  in  number  that  the  places 
occupied  by  them  are  recognizable  in  haematoxylin-eosin  preparations  as  clear  spaces 
in  this  portion  of  the  cell.  This  appearance  marks  the  transition  phase  from  the  rest- 
ing condition  of  Castellant's  observations  to  the  more  loaded  condition  of  the  third 
hour  of  digestion,  and  corresponds  exactly  to  what  I  (1898)  have  found  to  be  the  case 
under  similar  experimental  conditions  in  the  pyloric  glands  of  the  cat.  The  explana- 
tion is  that  the  cell  when  it  passes  from  the  resting  to  the  active  phase  begins  to 
transform  rapidly  into  mucigen  the  reserve  material  contained  in  its  basal  cytoplasm, 
the  product  of  this  transformation  making  its  appearance  in  the  space  between  the 
old  secretion  and  the  nucleus.  During  the  first  hours  of  digestion  this  transforma- 
tion of  antecedent  substance  into  mucigen  goes  on  more  rapidly  than  either  the  secretion 
of  the  mucin  from  the  cell  or  the  repair  of  the  basal  cytoplasm  from  which  it  is  formed. 
The  result  is  the  increase  in  reserve  secretion  in  the  cell.  A  cell  in  this  condition  of 
maximum  loading  presents  three  distinct  zones ;  a  narrow  basal  zone  of  protoplasm 
containing  the  now  slightly  flattened  nucleus;  then  the  proximal  mass  of  secretion, 
subdivided  by  coarse  trabeculas  of  cytoplasm ;  then  the  third  zone,  with  which  it  is 
continuous  and  into  which  it  passes  by  gradual  transition.  The  third  zone  contains 
the  distal  mass  of  secretion  along  the  free  border  of  the  cell  and  is  remarkable  for  the 
extreme  delicacy  of  the  cytoplasmic  threads  which  penetrate  it. 

The  cells  of  the  glands  of  Brunner  of  the  rat  may  therefore  present  one  of  three 
conditions  according  to  the  phase  of  activity.  Either  there  is  one  narrow  mass  of 
secretion  along  the  free  border ;  or  there  are  two  distinct  masses  of  secretion,  one  along 
the  free  border  and  one  in  the  interior  of  the  cell;  or,  finally,  there  is  a  single  continuous 
mass  of  secretion  which  shows  evidences  in  the  structure  of  the  included  cytoplasmic 
trabeculse  of  its  having  been  produced  by  the  fusion  of  two  masses  originally  distinct. 

The  cells  of  the  pyloric  glands  of  the  rat  differ  from  those  of  the  glands  of  Brunner 
in  the  same  way  as  do  the  corresponding  structures  in  the  muskrat,  dormouse,  and 
deer  mouse.  The  cells  of  the  glands  of  Brunner  are  from  13.3  ft  to  17.2  /*,  and  those 
of  the  pyloric  glands  from  8.9^  to  10.8 /*  in  height,  although  an  occasional  cell  may 
reach  a  height  of  13  p.  The  averages  are  15.7  ft  for  the  glands  of  Brunner,  and  9/t  for 
the  pyloric  glands.  The  differences  of  size  are  less  obvious  when  both  glands  are  in 
the  fully  loaded  condition. 

309 


34          THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNER 

The  secretion  of  the  glands  of  the  pyloric  region  forms  a  narrow  band  along  the 
lumen  which  is  much  more  compact  in  structure  than  the  secretion  in  the  glands  of 
Brunner,  and  like  the  contents  of  the  theca  in  the  gastric  epithelium  cell,  retains  some 
color  in  sections  stained  in  iron  ha?matoxylin,  in  which  the  secretion  of  the  Brunner's 
glands  are  colorless.  It  also  stains  more  intensely  blue  in  Mann's  methyl  blue-eosin. 
The  basal  cytoplasm  is  more  granular  in  appearance,  and  the  oval  nucleus  is  larger 
and  richer  in  chromatin,  than  in  the  cells  of  the  glands  of  Brunner. 

The  glands  of  Brunner  and  the  pyloric  glands  of  the  mouse  correspond  so  closely 
in  structure  and  staining  reactions  with  those  of  the  rat,  that  they  do  not  call  for 
special  description. 

VI.  THE  GLANDS  OF  BRUNNER  OF  THE  ARTIODACTYLA 

The  topography  of  the  glands  of  Brunner  of  the  Ungulates  has  been  recently 
studied  by  Hock  (1899).  In  the  horse  he  found  the  glands  to  extend  the  enormous 
distance  of  seven  meters  into  the  intestine.  In  the  pig  and  the  sheep — two  of  the  four 
genera  of  the  Artiodactyla  examined  by  him — they  were  also  of  considerable  extent : 
40  cm.  in  the  six-weeks-old  pig,  and  between  30  cm.  and  40  cm.  in  the  sheep.  In  a 
young  goat  two  or  three  weeks  old  he  found  the  glands  to  extend  only  4  cm.  into  the 
duodenum.  For  the  ox  he  gives  no  measurements. 

In  my  studies  the  Artiodactyla  are  represented  by  the  sheep  and  pig,  which  are 
especially  interesting  because  they  represent  the  two  extremes  of  specialization  of  the 
stomach  of  the  recent  Artiodactyla,  and  because  they  present  differences  in  the  relation 
of  the  pyloric  glands  to  the  glands  of  Brunner  which  may  be  compared  to  those  shown 
by  the  Rodentia  with  simple  stomachs  and  complex  stomachs  respectively.  In  the  pig, 
in  which  the  stomach  presents  the  simplest  form  found  in  the  group,  the  two  kinds  of 
glands  resemble  one  another  very  closely ;  in  the  sheep,  with  a  highly  specialized  stom- 
ach, the  two  kinds  of  glands  are  very  different.  They  are  further  of  interest  because 
of  Kuczynski's  failure  to  stain  the  secretion  by  any  of  the  methods  he  employed. 

As  far  as  the  arrangement  and  topography  of  the  glands  are  concerned,  Hock's 
excellent  description  leaves  little  to  be  desired.  In  the  pig,  according  to  him,  the 
glands  of  Brunner  are  the  direct  continuation  of  the  enormously  developed  pyloric 
glands,  which  at  the  summit  of  the  pyloric  sphincter  begin  to  divide  more  freely  and 
extend  more  deeply,  forming  new  lobules  which  completely  fill  the  tunica  mucosa  and 
open  by  short  tortuous  ducts  into  the  foveola  gastricse.  Presently  they  exceed  the 
limits  of  the  mucosa  and  extend  over  into  and  fill  the  submucosa.  For  about  1£  cm., 
according  to  Hock,  the  lamina  muscularis  mucossB  is  not  present  as  a  distinct  layer, 
but  the  fibers  are  dispersed  among  the  lobules  of  the  glands,  to  the  muscular  invest- 
ment of  which  the  pyloric  sphincter  also  contributes  fibers.  For  a  distance  of  20  cm. 
from  the  pylorus  the  glands  are  described  as  forming  a  compact  mass,  completely  filling 
the  submucosa.  He  finds  that  the  ducts  at  the  beginning  of  the  zone  discharge 
into  the  gastric  foveolss ;  beyond  the  point  of  the  first  appearance  of  the  glandulse 

310 


ROBERT  RUSSELL  BENSLEY  35 

intestinales  of  Lieberktihn,  they  empty  almost  exclusively  into  the  latter.     A  few 
independent  ducts,  however,  are  present. 

The  large  glandular  tubules  are  composed  of  large  cylindrical  cells,  18  ju-21  fi  in 
height,  surrounding  a  very  narrow  lumen.  The  nucleus  is  flattened  or  crescentic  and 
placed  in  the  base  of  the  cell.  The  body  of  the  cell  exhibits  a  faintly  staining  network 
containing  the  secretion.  Kuczynski  (1890)  was  unable  to  obtain  any  specific  staining 
of  this  secretion  by  the  methods  he  employed.  He  was  also  unsuccessful  in  attempting 
to  stain  the  secretion  of  the  similar  cells  of  the  pyloric  glands,  although  he  remarks 
that  the  pyloric  glands  near  the  fundus  zone  stain  with  Victoria  blue.  He  concluded 
that  if  they  contain  any  mucin  it  was  not  their  exclusive  constituent.  By  the  tech- 
nique recommended  at  the  beginning  of  this  article,  I  have  succeeded  in  staining  the 
secretion  of  both  the  pyloric  glands  and  the  glands  of  Brunner  intensely  in  muchse- 
matein  and  in  mucicarmine.  When  so  stained  the  meshes  of  the  cytoplasmic  network  of 
the  body  of  the  cell  are  found  to  be  filled  with  a  compact  mass  of  small  granules. 
Staining  in  indulin-eosin-aurantia  mixture  also  gave  successful  results.  There  is, 
therefore,  no  adequate  reason  for  supposing  that  the  cells  of  the  glands  of  Brunner  of 
the  pig  are  essentially  different  in  function  from  those  of  other  mammals. 

In  the  sheep  the  differences  between  the  glands  of  Brunner  and  the  pyloric  glands 
are  very  striking,  and  I  have  found  that  even  with  the  solutions  which  I  have 
employed  with  success  on  other  mammals  the  secretion  of  the  Brunner' s  glands  stains 
with  difficulty. 

The  pyloric  glands  of  the  sheep  are  simple  tubes  composed  of  somewhat  narrow 
triangular  cells  12.5  /J,  to  17 /*  in  height  with  nuclei  round,  oval,  or  crescentic  accord- 
ing to  the  shape  and  secretory  condition  of  the  cell.  Around  the  nucleus  is  a  very 
small  amount  of  finely  reticular  cytoplasm.  The  body  of  the  cell  is  transparent,  and 
finely  reticular.  The  secretion  forms  a  continuous  mass,  and  stains  readily  and  deep- 
ly in  muchsematein  and  mucicarmine. 

The  glands  of  Brunner  are  exceedingly  large  tubules,  with  wide  lumina  sur- 
rounded by  cylindrical  cells  16  /t  to  22  p  in  height.  The  nucleus  in  these  cells  is 
spherical  or  oval,  slightly  cupped  on  the  side  directed  toward  the  lumen,  and  located  in 
the  proximal  end  of  the  cell.  The  whole  of  the  cell  between  the  nucleus  and  the 
lumen  is  filled  with  secretion  which  is  distinctly  divided  into  a  proximal  and  distal 
mass  in  many  of  the  cells.  The  secretion  stains  in  muchsematein,  but  much  more 
slowly,  and  less  intensely,  than  that  of  the  pyloric  glands.  The  differences  in  shape 
and  character  of  the  tubules  and  cells  of  the  glands  of  Brunner  are  particularly  obvious 
opposite  the  sphincter  pylori  where  glands  of  Brunner  occur  in  the  mucous  membrane 
side  by  side  with  the  pyloric  glands.  Very  striking  at  this  point  is  the  contrast,  in 
muchaematein  preparations,  between  the  deeply  stained  narrow  tubules  of  the  pyloric 
glands  and  the  faintly  stained  wide  tubules  of  the  glands  of  Brunner.  The  difference 
in  staining  capacity  does  not,  as  will  be  pointed  out  later,  imply  a  difference  in  the 
amount  of  mucin  secreted  by  the  cells. 

311 


36  THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNER 


VII.    THE  GLANDS  OP  BRUNNER  OF  MAN 

The  material  for  this  study  consisted  of  the  duodenum  and  a  portion  of  the 
jejunum  of  an  executed  criminal,  a  young  man  about  thirty  years  of  age.  The  material 
was  obtained  about  forty-five  minutes  after  death  and,  although  the  epithelium  of  the 
free  surface  and  portions  of  the  villi  were  lost  in  places,  proved  to  be  in  other  respects 
excellently  preserved.  A  strip  from  end  to  end  of  the  duodenum  was  fixed  in  alcoholic 
sublimate  bichromate  mixture  and  the  rest  in  70  per  cent,  alcohol.  For  comparison  a 
second  duodenum  obtained  for  the  writer  from  the  body  of  a  woman  seventy  years  of 
age,  and  fixed  in  alcoholic  sublimate  bichromate,  was  studied.  In  the  latter  marked 
cell-atrophy  was  exhibited  by  the  glands  of  Brunner,  but  some  interesting  facts  were 
obtained  as  to  the  mode  of  accumulation  of  the  secretion  in  the  cell. 

The  observations  of  the  writer  confirm  in  the  main  those  of  Renaut  (1879), 
Schaffer  (1891),  and  Castellant  (1898)  as  to  the  distribution  of  the  glands  of  Brunner 
in  the  intestine  of  man. 

The  glands  make  their  appearance  in  the  mucosa  and  submucosa,  opposite  the 
summit  of  the  pyloric  sphincter,  at  the  point  where  the  first  intestinal  gland  of  Lieber- 
kuhn  appears.  There  is  for  a  short  distance,  about  2.5mm.  in  my  material,  a  slight 
mingling  of  intestinal  and  gastric  glands  as  observed  by  Bohin  and  von  Davidoff  (1895), 
and  confirmed  by  Castellant  ( 1898).  In  this  region,  however,  only  a  few  pyloric  glands 
are  visible,  and  in  some  of  these  goblet  cells  occur  among  the  gastric  epithelial  cells. 

The  glands  of  Brunner  located  in  the  mucous  membrane  at  this  point  form  groups 
of  radiating,  slightly  wavy,  branched  tubules,  clustered  around  the  base  of  a  gland  of 
Lieberkuhn,  or  of  a  foveola  gastrica  into  which  they  open.  They  are  not  in  this  region 
clearly  marked  off  into  lobules,  and  are  a  direct  continuation  of  the  pyloric  glands 
which,  as  many  writers  have  pointed  out,  exhibit  a  tendency  to  richer  branching  near 
the  beginning  of  the  duodenum. 

In  the  pars  superior  of  the  duodenum  from  the  first  individual  the  surface  of  the 
mucosa  presented  a  somewhat  mammillated  appearance,  owing  to  the  occurrence  in  it 
of  many  large  solitary  follicles  ( noduli  lymphatici  solitarii).  In  sections  these  solitary 
follicles  form  interruptions  at  regular  intervals  in  the  continuity  of  the  glandular 
elements  of  the  mucous  membrane,  as  may  be  seen  in  Plate  XXIV,  Figs.  14  and  15. 
This  fact  gives  in  sections  an  appearance  of  regular  grouping  of  the  glands  located  in 
the  tela  submucosa  as  well  as  of  those  in  the  mucous  membrane,  because,  obviously, 
the  ducts  of  the  former  must  open  to  the  surface  between  the  solitary  follicles  and  the 
lobules  of  the  glands  must  be  arranged  in  a  radial  fashion  around  the  ducts.  This 
appearance  is  well  illustrated  in  Fig.  15,  where  the  lobules  of  the  group  in  the  sub- 
mucosa spread  out  in  a  fan-like  fashion  from  the  point  in  the  mucosa  where  their 
terminal  ducts  are  located. 

In  the  pars  superior  duodeni  the  glands  of  Brunner,  as  described  by  Renaut 
(1879)  and  confirmed  by  Schaffer  (1891)  and  Castellant  (1898),  form  two  groups, 

312 


ROBERT  RUSSELL  BENSLEY  37 

one  located  in  the  mucous  membrane,  the  other  in  the  submucosa.  The  former,  except 
for  the  interruptions  caused  by  the  lymphatic  nodules,  form  an  almost  continuous  layer 
occupying  exclusively  the  outer  half  of  the  mucous  membrane,  the  inner  half  being 
occupied  by  the  glands  of  Lieberkuhn  and  the  villi.  The  lobulation  is  not  very  strik- 
ing, although,  as  shown  in  Fig.  14,  the  groups  of  glands  which  empty  into  a  single 
duct  may  be  easily  recognized.  These  groups  are  somewhat  elliptical  or  triangular  in 
section,  the  long  axes  being  perpendicular  to  the  surface  of  the  mucous  membrane. 
From  the  inner  end  of  each  group  one,  two,  or  more  ducts  emerge,  which  either  join 
to  form  a  single  duct,  or  open  separately  into  the  same  gland  of  Lieberktihn  or  into 
side  branches  of  the  latter. 

Each  group  is  composed  of  a  cluster  of  tubules,  which  are  the  primary  branches 
of  the  duct,  and  of  the  numerous  ramifications  of  the  latter.  The  most  prevalent 
mode  of  branching  is  as  follows:  the  duct  divides  near  its  origin  into  a  tassel-like 
group  of  wavy  tubules  which  pass  outward  in  the  direction  of  the  lamina  muscularis 
mucosa3.  Each  of  these  tubules  gives  off  on  all  sides  radial  descending  branches, 
which  in  their  turn,  after  a  very  short  course,  subdivide  and  terminate  either  as  short 
tubules  of  the  same  diameter  as  the  parent  tubules,  or  as  slightly  expanded,  elongated, 
pear-shaped  acini.  Some  of  the  groups  extend  through  the  interrupted  muscularis 
mucosse  to  form  lobules  or  groups  of  lobules  in  the  inner  layer  of  the  tela  submucosa. 

The  group  of  glands  in  the  submucosa  is  composed  of  elliptical  and  fusiform 
lobules  of  small  size,  placed  with  their  long  axes  nearly  parallel  to  the  free  surface  of 
the  duodenum.  These  lobules  are  confined  to  the  inner  layer  of  the  tela  submucosa, 
there  being  usually  an  outer  layer  nearest  the  tunica  muscularis  free  from  glands  and 
containing  aggregations  of  adipose  tissue.  The  lobules  are  not  all  independent  of  one 
another,  several  being  often  strung  out  along  the  same  tortuous  duct.  Again,  many  of 
the  larger  lobules  are  subdivided  into  marginal  lappets  which  represent  the  groups  of 
branches  clustered  around  each  of  the  radial  branches  of  the  principal  duct  of  the  lobule. 

The  lobules  of  the  submucous  group  of  glands  are  derived  from  three  sources. 
Some  consist  of  the  continuation  into  the  submucosa  of  groups  of  tubules,  the  main 
bulk  of  which  is  located  in  the  mucous  membrane.  In  a  second  series  a  tubule,  after 
giving  off  a  number  of  branches  in  the  mucous  membrane,  passes  through  an  aperture 
in  the  lamina  muscularis  mucosae,  and  gives  rise  to  one  or  several  lobules  in  the  submu- 
cosa. In  the  third  series  a  duct  of  variable  size  passes  directly  from  the  bottom  or  side 
of  a  gland  of  Lieberkuhn  to  the  submucosa,  where  it  terminates  in  a  lobule  or  a  series 
of  lobules.  In  the  pars  superior  duodeni  of  the  cases  examined  the  second,  in  the  pars 
horizoutalis  and  pars  ascendens  of  the  organ  the  third,  was  the  prevailing  type. 

The  point  of  junction  with  the  gland  of  Lieberkuhn  is  a  variable  one,  but  I  have 
not  observed,  in  either  of  the  two  duodena  examined,  a  single  instance  of  the  duct 
reaching  the  free  surface  independently  of  the  intestinal  glands,  although  that  such 
cases  do  occur,  is  shown  by  the  observations  of  Schaffer  and  Castellant. 

As  regards  the  distribution  of  the  glands  of  Bruuner  in  man,  the  observations  of 


38          THE  STRUCTURE  OP  THE  GLANDS  OF  BKUNNEB 

the  writer  confirm  the  description  given  by  Castellant  (1898),  except  with  respect  to 
their  downward  extent.  In  this  case  the  glands  extend  only  within  about  3.5  cm.  of 
the  duodenojejunal  flexure;  in  Castellant1  s  case  isolated  lobules  were  found  in  the 
upper  part  of  the  jejunum. 

From  the  beginning  of  the  pars  descendens  duodeni  downward  the  glands  are 
progressively  reduced  in  bulk  and  tend,  as  Castellant  observed,  to  become  located  in 
the  plicae  circulares  (Kerkringi),  although  not  wholly  confined  to  the  latter.  In  the 
lower  part  of  the  duodenum  they  are  reduced  to  scattered  small  lobules.  Throughout, 
however,  there  are  tubules  in  the  tunica  mucosa  as  well  as  in  the  submucosa,  although 
the  latter  predominate.  Castellant  remarks  concerning  these  tubules  of  the  mucous 
membrane:  "Elles  cessent  mfime  presque  comple"tement  an  niveau  de  1' union  de  la 
premiere  portion  du  duodenum  avec  la  seconde ;  on  n'  en  retrouve  plus  qu'  accidentelle- 
ment  au  deli" — indicating  that  he  observed  them  in  the  lower  portion  of  the  duode- 
num, but  in  smaller  numbers  than  in  the  material  described  above. 

In  each  of  the  lobules  of  the  submucous  group  may  be  distinguished  a  central 
tubule  which  is  the  duct  of  the  lobule.  From  this  duct,  which  may  be  extremely 
tortuous  in  its  course,  come  off  numerous  side  branches  of  various  lengths  and  com- 
plexity of  secondary  branching.  After  passing  through  one  lobule,  a  duct  may  enter 
a  second  and  a  third,  branching  in  each  in  a  similar  way ;  or  some  of  the  side  branches 
may  pass  out  and  form  the  central  duct  of  accessory  lobules.  Often  the  central  duct 
of  a  lobule  may  be  locally  enlarged,  as  may  be  seen  in  some  parts  of  Fig.  15. 

The  ducts  pass  through  openings  in  the  muscularis  mucosae  sometimes  singly, 
more  often  in  groups,  and  empty  into  the  bottoms,  sides,  or  branches  of  the  glands  of 
Lieberkuhn.  In  the  submucous  as  in  the  mucous  group,  the  terminal  branches  of  the 
secreting  tubules  are  short  tubules  of  the  same  size  as  the  main  branches,  or  elongated, 
pear-shaped  acini.  In  both  cases  they  are  formed  of  cells  similar  to  those  forming  the 
ducts  and  their  various  branches. 

All  the  tubules  of  the  glands  of  Brunner  of  man  are  provided  with  a  delicate 
basement  membrane  composed  of  reticulum.  The  ducts  and  tubules  are  formed  of 
somewhat  rectangular  epithelial  cells,  15  /*  to  21  p  in  height,  uniform  in  type  through- 
out the  gland,  but  with  some  differences  of  structural  details  in  different  parts.  In  the 
terminal  tubules  in  the  material  from  the  young  subject,  the  cells  are  of  the  type  repre- 
sented in  Plate  XXII,  Figs.  11  and  12.  The  nucleus  is  crescentic  or  flattened  in  form, 
and  is  located  in  the  outer  end  of  the  cell.  The  body  of  the  cell  contains  a  network  com- 
posed of  extremely  fine  cytoplasmic  fibrils  forming  large  meshes  in  which  the  secretion 
of  the  cell  is  contained.  In  the  center  of  the  cell  the  cytoplasm  forms  a  network  of 
smaller  meshes  and  coarser  trabeculse  corresponding  to  the  band  of  cytoplasm 
separating  the  two  masses  of  secretion  in  the  cells  of  the  opossum,  cat,  mink,  etc. 

As  may  be  seen  from  Figs.  14  and  15,  which  are  half-tone  reproductions  of 
photomicrographs  of  specimens  stained  in  strong  muchffimatein,  the  glands  of 
Brunner  stain  even  more  intensely  in  this  solution  than  the  goblet  cells  of  the 

314 


ROBERT  RUSSELL  BENSLEY  39 

intestinal  glands.  In  strong  mucicarmine  a  similar  result  is  obtained.  The  appear- 
ance of  the  stored-up  secretion  when  stained  in  muchsematein  depends  on  the  mode  of 
fixation  and  subsequent  treatment.  In  the  material  fixed  in  alcoholic  bichromate  sub- 
limate, imbedded  in  celloidin,  sectioned  and  stained,  without  passing  through  water, 
the  secretion  is  in  the  form  of  minute  granules  of  smaller  size  and  less  closely  packed 
than  those  in  cells  from  the  glands  of  Brunner  of  the  opossum.  In  sections  cut  in 
paraffin,  fastened  to  the  slide  by  the  water  method,  and  stained  with  muchaematein, 
the  secretion  presents  itself  in  the  cell  in  the  form  of  a  coarse-meshed  network.  A 
result  similar  to  the  latter  is  obtained  with  material  fixed  in  70  per  cent,  alcohol,  except 
that  the  meshes  of  the  mucin  network  are  much  larger  and  are  formed  of  thicker 
trabeculae. 

In  the  ducts  the  cells  are  similar  to  those  in  the  tubules  and  acini;  indeed,  many 
of  the  ducts  of  the  small  lobules  are  indistinguishable  from  the  other  tubules  forming 
the  lobules  except  by  the  method  of  tracing  them  out  in  serial  sections.  In  the  larger 
ducts,  however,  and  particularly  in  locally  dilated  portions  of  them,  the  cells,  while 
similar  to  those  of  the  acini,  tend  to  be  more  protoplasmic  in  nature.  In  such  cells 
the  division  of  the  secretion  into  two  masses  and  the  transverse  band  of  cytoplasm 
separating  them  are  particularly  obvious,  and  the  cell  presents  a  structure  exactly 
comparable  to  that  shown  in  Fig.  2,  which  is  taken  from  the  cells  of  the  opossum. 
Zimmermann  (1898)  described  and  figured  this  condition  in  the  cells  of  the  glands  of 
Brunner  of  man,  but  did  not  recognize  the  fact  that  the  outer  clear  zone  near  the 
nucleus  represented  a  second  accumulation  of  secretion  in  that  part  of  the  cell. 

In  passing  from  a  duct  to  a  side  branch  of  it,  there  is  a  gradual  transition  from 
this  more  cytoplasmic  type  of  cell  with  spherical  nucleus  and  two  distinct  masses  of 
secretion  to  the  secretion-filled  cell  with  a  single  continuous  mass  and  crescentic 
nucleus. 

A  similar  transition  occurs  in  the  tubules  of  the  glands  located  in  the  mucosa.  A 
small  gland  from  this  source,  together  with  a  portion  of  the  gland  of  Lieberkuhn  into 
which  it  opens,  is  shown  in  Fig.  12.  In  the  gland  of  Lieberkuhn  in  this  figure  the 
three  typical  elements — cylindrical  cells,  goblet  cells,  and  one  Paneth  cell — are  seen. 
The  change  to  the  epithelium  of  Brunner's  gland,  as  indicated  by  Schaffer  (1898),  is 
abrupt,  i.  e.,  there  are  no  intermediate  stages  between  it  and  the  intestinal  epithelial 
elements.  In  the  Brunner's  gland,  however,  a  gradual  transition  is  to  be  observed 
from  the  cell  with  a  narrow  band  of  secretion  along  the  lumen,  a  large  mass  of  cyto- 
plasm, and  a  spherical  nucleus,  to  the  secretion-filled  cell  with  a  crescentic,  basally 
situated  nucleus.  In  some  of  the  latter  the  remains  of  the  band  of  cytoplasm  separat- 
ing the  two  primary  masses  of  secretion  may  be  clearly  seen. 

A  point  of  considerable  interest  is  the  occurrence  in  the  human  glands  of  Brunner 
of  a  very  small  number  of  parietal  cells  exactly  similar  to  those  seen  in  the  gastric 
glands.  These  cells  occur  in  very  small  numbers,  but  their  structure  is  so  character- 
istic that  there  can  be  no  doubt  of  the  correctness  of  their  identification.  They 

315 


40          THE  STRUCTURE  OP  THE  GLANDS  OF  BRUNNER 

contain  distinct  intracellular  ducts,  and  exhibit  the  three  characteristic  zones  of 
structures  described  by  Zimmermann  (1898)  for  the  parietal  cells  of  the  stomach.  As 
in  the  latter  the  nuclei  may  be  multiple. 

The  cells  of  the  pyloric  glands  in  man  resemble  very  closely  in  size  and  structure 
those  of  the  glands  of  Brunner.  In  general,  in  the  former  the  subdivision  of  the 
secretion  into  two  masses  is  more  obvious  and  the  proximal  mass  contains  coarser 
cytoplasmic  trabeculae. 

The  cells  of  the  glands  of  Brunner  of  the  old  subject  were,  as  has  already  been 
remarked,  considerably  atrophied.  They  measured  12  /*  to  14  n  in  height.  The 
lumen  showed  a  corresponding  enlargement.  In  most  of  the  tubules  the  secretion 
stainable  in  strong  muchsematein  was  confined  to  a  narrow  zone  less  than  2  n  in  width 
along  the  lumen.  The  rest  of  the  cell  was  occupied  by  a  continuous  mass  of  cytoplasm 
containing  the  oval  nucleus.  In  some  of  the  cells,  however,  a  second  small  proximal 
mass  of  secretion  occurred  in  the  midst  of  this  cytoplasm  between  the  nucleus  and  the 
narrow  distal  mass,  and  in  a  few  tubules  the  two  had  become  confluent,  forming  a 
single  large  mass  of  secretion,  filling  all  of  the  space  between  the  now  flattened  nucleus 
and  the  lumen. 

VIII.    DISCUSSION  OF  RESULTS 

The  results  of  this  investigation  show  that  there  is  a  remarkable  uniformity  in 
the  nature  and  structure  of  the  glands  of  Brunner  of  many  mammals.  In  eighteen  out 
of  the  nineteen  genera  examined  the  glands  are  of  the  pure  mucous  type.  This  con- 
clusion is  based  on  the  structure  of  the  cells  of  the  glands,  and  on  their  staining  and 
microchemical  properties.  The  evidence,  which  is  partly  negative,  partly  positive, 
may  be  briefly  summed  up  as  follows: 

The  cells  of  the  glands,  when  examined  fresh  in  serum  or  normal  salt  solution,  do 
not  show  easily  visible  secretion-granules.  The  granules  (droplets?)  of  secretion  like 
those  of  known  mucous  glands  correspond  so  closely  in  refractive  power  with  the 
mounting  media  that  they  are  almost  invisible. 

The  cells  when  fixed  and  stained  do  not  contain  basal  filaments  (prozymogen), 
and  the  microchemical  test  for  organic  iron  indicates  the  presence  of  only  a  relatively 
small  amount  of  cytoplasmic  nucleoproteid.  Serous  cells  from  other  sources,  on  the 
other  hand,  show  the  presence  of  a  large  amount  of  cytoplasmic  nucleoproteid,  either 
in  the  form  of  the  so-called  basal  filaments  (composed  largely  of  the  nucleoproteid 
prozymogen)  or  in  the  form  of  prozymogen  diffused  in  the  basal  cytoplasm. 

The  granules  of  zymogen  in  the  pancreatic  and  gastric  ferment-secreting  cells 
stain  strongly  in  iron  haematoxylin.  The  secretion  of  the  cells  of  the  glands  of  Brun- 
ner remain  colorless  in  this  stain. 

A  more  positive  and  selective  stain  for  the  granules  of  zymogen  of  the  stomach 
and  pancreas,  Reinke's  neutral  gentian,  as  modified  by  the  writer  (1900),  also  gives 
negative  results  with  the  cells  of  the  glands  of  Brunner. 

316 


ROBERT  RUSSELL  BENSLEY  41 

The  secretion  granules  of  the  cells  of  the  glands  of  Brunner  give  no  reaction 
when  tested  by  Macallum's  method  for  the  microchemical  detection  of  organic  phos- 
phorus. The  progress  of  this  reaction  is  easily  controlled,  in  the  case  of  the  glands 
of  Brunner,  by  observing  the  effect  on  the  granules  in  adherent  sections  of  the 
pancreas,  which  give  a  positive  reaction  for  organic  phosphorus  after  treatment  for  two 
hours  with  nitric  acid  ammonium  molybdate.  The  results  with  this  test  in  the  glands 
of  Brunner,  with  the  exception  of  the  dark  tubules  of  the  glands  in  the  rabbit,  are 
absolutely  negative. 

Not  only  do  the  cells  of  Brunner  not  contain  the  chemical  substances  which  it  is 
possible  to  recognize  in  the  serous  cell  either  by  examining  the  fresh  cell  or  by  employ- 
ing staining  and  microchemical  methods,  but,  on  the  contrary,  there  is  positive  evi- 
dence that  they  contain  something  else,  which  we  have  good  reason  to  believe  is  mucin. 

The  secretion  contained  in  the  cells  of  the  glands  of  Brunner  stains  with  uniform 
facility,  if  certain  precautions  are  taken,  in  Mayer's  alcoholic  muchaematein  and  muci- 
carrnine.  With  muchajmatein  the  precautions  necessary  to  success  are  as  follows: 

If  the  dilute  solution  recommended  by  Mayer  is  employed,  the  sections  cut  in 
paraffin  should  be  transferred,  without  attaching  them  to  slides,  to  benzole,  thence 
to  absolute  alcohol,  thence  directly  to  the  staining  solution.  After  five  minutes  in  the 
latter,  they  are  washed  with  70  per  cent,  alcohol,  dehydrated,  cleared,  and  mounted. 

A  stronger  solution  (having  the  following  formula:  haematein,  1  g.,  aluminium 
chloride,  0.5  g.,  70  per  cent,  alcohol,  100  c.c.)  gives  better  results,  and  can  be  used  on 
sections  fastened  to  the  slides  or  on  celloidin  sections  with  certainty  of  S|>eedy  and 
satisfactory  results.  The  degree  of  acidity  of  this  solution  is  of  some  importance. 
The  writer  is  in  the  habit  of  reducing  the  acidity  by  diluting  his  alcohol  with  tap 
water  containing  calcium  bicarbonate.  After  the  solution  so  prepared  has  stood 
for  a  week,  it  is  tested  on  a  section.  If  the  resulting  stain  is  slightly  diffuse,  a  10  per 
cent,  solution  of  nitric  acid  is  added,  a  drop  at  a  time,  the  staining  properties  being 
tested  on  a  section  after  the  addition  of  each  drop  of  acid.  This  is  kept  up  until 
the  correct  reaction  is  obtained.  The  solution  so  prepared  is  employed  as  follows : 

The  sections  cut  in  paraffin  and  fastened  to  the  slide  by  the  albumen  or  by  the 
water  method  are  treated  with  benzole  followed  by  absolute  alcohol.  The  slide  having 
been  placed  on  the  stage  of  the  microscope,  a  drop  of  the  staining  solution  is 
applied  to  the  section,  and  the  latter  is  watched  under  the  microscope  until  a  proper 
depth  of  color  is  obtained  in  the  secretion  within  the  cells.  It  is  then  rapidly  washed 
in  70  per  cent,  alcohol,  dehydrated,  cleared  in  benzole,  and  mounted  in  benzol  balsam. 

If  the  staining  is  prolonged  and  the  solution  is  not  renewed  from  time  to  time, 
the  sections  after  attaining  a  maximum  depth  of  color  will  slowly  fade  out  again, 
probably  owing  to  reduction  in  the  acidity  of  the  solution  by  the  absorption  of 
ammonia  from  the  atmosphere.  Sections  should  not  be  washed  in  water  after  staining, 
as  this  procedure  completely  removes  the  stain  from  the  mucous  cells. 

This  stronger  inuchsematein  solution  stains  deep  blue  the  secretion  contained  in 

317 


42          THE  STRUCTURE  OF  THE  GLANDS  OF  BBUNNER 

cells  from  the  following  sources:  mucous  cells  from  the  submaxillary,  sublingual, 
lingual,  palatine,  tracheal,  and  oesophageal  glands;  the  gastric  epithelial  cells;  the 
cells  of  the  cardiac  glands  of  the  stomach ;  the  cells  of  the  pyloric  glands ;  the  neck 
chief  cells  of  the  f undus  glands  of  the  stomach ;  goblet  cells ;  and  the  cells  of  the 
glands  of  Brunner  (except  the  dark  tubules  of  the  rabbit's  glands).  It  docs  not  slain 
the  secretion  in  cells  from  the  following  sources ;  demilune  cells  of  the  salivary  glands ; 
the  cells  of  the  parotid  gland;  the  serous  cells  of  the  submaxillary  or  sublingual 
glands;  the  serous  portions  of  the  palatine  glands  and  tracheal  glands;  nor  the  fer- 
ment-forming cells  of  the  pancreas  and  of  the  fundus  glands  of  the  stomach. 

An  idea  of  the  intensity  of  the  resulting  color  got  by  this  method  may  be  obtained 
from  Figs.  14  and  15,  which  are  half-tone  reproductions  of  photomicrographs  of  sec- 
tions of  the  human  glands  of  Brunner  stained  in  stronger  muchsematein.  An  equally 
strong  stain  was  obtained  in  the  glands  of  Brunner  of  all  the  animals  examined,  with 
the  single  exception  of  the  sheep,  in  which  the  secretion  stained  positively,  but  more 
slowly  and  with  less  intensity. 

For  mucicarmine  the  conditions  of  success  are  that  the  solution  be  employed 
undiluted  in  the  form  of  Mayer's  stock  solution,  and  that  it  be  freshly  prepared.  In 
the  writer's  hands  the  solution,  after  twenty-four  to  forty-eight  hours,  refuses  to  stain 
and  cannot  be  filtered.  The  solution  is  to  be  applied  in  exactly  the  same  way  as 
muchsematein  and  gives  similar  results,  both  on  the  glands  of  Brunner  and  on  the  other 
glands  mentioned.  In  view  of  the  results  in  the  several  glands  of  known  character 
which  are  enumerated  above,  we  are  justified  in  concluding  that  the  solutions  employed 
as  recommended  do  stain  mucous  cells  and  do  not  stain  serous  (zymogenic)  cells. 

In  view  of  Mayer's  observation  that  the  clear  cells  of  the  submaxillary  gland  of 
the  hedgehog,  which  do  not  secrete  mucin,  stain  with  muchfematein,  some  conservatism 
must,  however,  be  exercised  in  interpreting  the  results.  It  is  obvious  that  no  absolute 
proof  of  the  mucous  character  of  the  glands  of  Bruuner  can  be  brought  forward  until 
a  positive  microchemical  test  for  the  various  mucins  is  devised,  or  until  some  one 
undertakes  and  completes  the  laborious  task  of  isolating  the  lobules  of  Brunner's 
glands  carefully  by  dissection  and  studying  them  by  the  ordinary  macrochemical 
methods.  The  mucous  nature  of  the  glands  is,  however,  supported  by  the  recent  work 
of  Ponomareff  (1902)  in  Pawlow's  laboratory,  who  isolated  a  portion  of  the  duodenum 
by  Thiry's  method  as  modified  by  Pawlow.  The  juice  obtained  was  colorless,  thick, 
and  very  viscid. 

Further  evidence  is,  however,  afforded  by  the  tests  applied  to  determine  the 
solubility  of  the  secretion  in  various  solutions.  This  is  accomplished  by  using  muchse- 
matein  as  an  indicator.  The  sections  are  fastened  to  the  slide  by  the  water  method, 
and  are  placed  in  the  solution  to  be  tested.  From  time  to  time  a  section  is  taken  out, 
washed  thoroughly,  and  stained  by  muchsematein.  By  this  means  it  has  been  deter- 
mined that  the  contents  of  the  cells  of  the  glands  of  Brunner  of  the  opossum  and  of 
man  are  soluble  in  weak  alkaline  solution,  insoluble  in  5  per  cent,  solution  of  hydro- 

318 


ROBERT  RUSSELL  BENSLEY  43 

chloric  acid  and  in  artificial  gastric  juice  containing  0.2  per  cent,  of  hydrochloric  acid. 

The  structure  of  the  cells  also  supports  the  conclusion  that  they  are  mucous  cells. 

The  cells  of  the  glands  of  Brunner  differ  in  structure  according  to  the  physio- 
logical phase  in  which  they  happen  to  be  when  examined.  Three  well-defined  stages 
may  be  discerned:  In  the  condition  of  maximum  loading  the  cells  are  large  and 
transparent.  They  contain  a  flattened  or  crescentic  nucleus,  located  in  the  base  of  the 
cell,  surrounded  by  a  small  quantity  of  finely  reticular  cytoplasm.  The  body  of  the 
cell  is  clear  and  shows  a  coarse  network  of  cytoplasmic  trabeculae  in  the  meshes  of 
which  the  secretion  is  lodged. 

In  the  intermediate  condition,  the  nucleus  is  more  oval  in  outline,  the  basal 
cytoplasm  is  greater  in  amount  and  the  body  of  the  cell  exhibits  two  distinct  secretory 
zones.  In  the  proximal  zone  the  granules  of  secretion  are  separated  from  one  another 
by  cytoplasmic  trabeculse  coarser  than  those  of  the  distal  zone.  (See  Fig.  2.) 

In  the  discharged  condition  the  nucleus  is  spherical  or  oval  and  nearer  the  center 
of  the  cell.  The  basal  cytoplasm  is  increased  in  amount.  The  secretion  may  be  con- 
fined to  a  mass  on  the  free  border  of  the  cell,  or  there  may  be  two  masses,  a  dense  one 
on  the  free  border  (referred  to  in  the  specific  descriptions  as  the  distal  mass)  and  a  less 
dense  one  (the  proximal  mass)  composed  of  smaller  granules,  in  the  interior  of  the  cell. . 

The  two  latter  conditions  may  be  reached  either  as  stages  in  the  discharge  of  the 
cell,  or  in  inverse  order,  as  stages  in  its  recovery  during  a  period  of  rest  after  discharge 
of  its  secretion. 

In  the  writer's  opinion,  the  obvious  subdivision  of  the  secretion  into  two  masses  is 
due  to  the  fact  that  the  new  secretion  is  formed  in  the  neighborhood  of  the  nucleus  in 
the  interior  of  the  cell.  This  may  be  due,  as  suggested  above,  to  the  action  of  enzymes 
produced  by  the  nucleus,  or  it  may  be  due  to  the  effect  of  the  presence  (of  which  the 
writer  has  not  yet  been  able  to  obtain  evidence)  in  these  cells  of  structures  similar  to 
the  so-called  trophospongium  observed  by  Holmgren  (1902)  in  various  epithelial  cells. 

A  similar  secretory  mechanism  has  been  shown  to  exist  in  the  various  mucous 
salivary  glands  by  the  studies  of  Maximow  (1901)  and  Kolossow  (1903).  Both  of 
these  writers  have  noticed  the  obvious  division  of  the  secretory  portion  of  mucous  cells 
into  two  zones,  and  Maximow  has  also  observed  the  new  formation  of  secretion  granules 
in  the  neighborhood  of  the  nucleus.  I  have  (1898,  1902)  demonstrated  similar  condi- 
tions in  the  cells  of  the  palatine  glands,  pyloric  glands,  cardiac  glands,  and  in  the 
mucous  neck  chief  cells  of  the  fundus  glands  of  mammals.  Krause  (1895)  has  also 
described  the  formation  of  new  secretion  near  the  nucleus  in  the  mucous  cells  of  the 
retrolingual  glands  of  Erinaceus. 

The  conclusion  that  the  glands  of  Brunner  are  mucous  glands  is  concurred  in  by 
a  number  of  writers  mentioned  in  the  introductory  paragraphs.  Castellant  (1898), 
Kuczynski  (1890),  and  Schaffer  (1891)  came  to  a  similar  conclusion,  with  some  reserva- 
tions. The  two  former,  using  various  synthetic  stains  and  ordinary  solutions  of 
hsematoxylin,  have  observed  that  the  secretion  of  the  glands  of  Brunner  of  different 

319 


44          THE  STRUCTURE  OF  THE  GLANDS  OF  BBUNNEB 

mammals,  and  indeed  of  different  tubules  of  the  same  animal,  stain  with  different 
degrees  of  facility.  They  conclude  that  the  depth  of  staining  indicates  the  amount  of 
mucin  present  in  the  cell,  and  that  some  cells  contained  a  great  deal  of  inucin,  others  a 
little,  and  still  others  none  at  all.  The  uniformly  intense  stain  obtained  by  the  writer 
by  means  of  his  muchsematein  technique  shows  that  this  conclusion  is  not  justified. 
The  cells  are  to  all  appearance  in  all  mammals  equally  engaged  in  inucin  secretion. 

Does  the  different  capacity  for  staining  in  these  synthetic  dyes  indicate,  as 
Schaffer  (1891)  thought,  a  difference  in  the  nature  of  the  mucins  formed?  It  is,  of 
course,  possible  that  this  is  the  case.  We  already  know  many  different  mucins,  nnd 
we  have  reason  to  suspect,  as  Huppert  (189G)  has  suggested,  that  there  is  a  great 
number  of  different  glycoproteids.  Although  it  is  possible  that  different  mucins  are 
secreted  by  the  glands  of  Brunner  in  different  mammals,  it  does  not  appear  to  me  to 
be  necessary  to  assume  that  this  is  the  case  in  order  to  explain  the  different  staining 
properties. 

It  is  known  that  the  mucous  cells  do  not  store  their  secretion  as  mucin,  but  as  a 
substance  (mucigen)  which  may  readily  be  transformed  into  mucin.  It  is  not  possible 
definitely  to  identify  the  granules  visible  in  the  cell  as  mucigen,  but  they  are  probably 
composed  of  one  of  the  antecedents  of  mucin,  and  not  of  mucin  itself.  It  is,  more- 
over, probable  that  the  transformation  of  the  substances  received  by  the  cell  into  niuciu 
is  not  accomplished  by  one  or  even  two  steps,  but  that  there  are  many  stages  in  this 
chemical  process.  Furthermore,  it  is  a  well-known  fact  that  similar  cells  from  differ- 
ent sources,  engaged  in  the  formation  of  the  same  product,  may  store  it  in  the  form  of 
different  antecedent  substances.  For  example,  the  chief  cells  of  the  glands  of  the 
gastric  fundus  of  the  rabbit  in  the  resting  condition  are  filled  with  zymogen  granules 
and  contain  little  prozymogen.  The  similar  cells  of  the  glands  along  the  greater  cur- 
vature contain  few  granules,  but  a  great  deal  of  prozymogen.  These  cells  differ,  as 
Langley  (1882)  pointed  out,  in  secretory  equilibrium. 

It  is  conceivable  that  mucous  cells  similarly  differ  in  secretory  equilibrium,  and 
that,  while  the  ultimate  product  of  their  secretory  activity  may  be  the  same  substance, 
they  contain  the  antecedent  substances  in  varying  proportions.  Some  such  explana- 
tion as  this  must  be  resorted  to,  in  order  to  explain  why  similar  cells  of  the  same  tubule 
differ  in  their  staining  capacity. 

The  glands  of  Brunner  of  the  rabbit  are  mixed  glands.  The  bulk  of  the  cells 
composing  the  tubules  are  mucous  cells  similar  in  all  important  respects  to  those  in 
other  mammals.  In  many  cases  the  dark  cells  forming  the  terminal  acini  or  tubules  are 
specifically  different  from  the  mucous  cells.  There  are  no  intermediate  stages,  and 
these  cells  do  not  under  any  conditions  contain  mucin  or  its  stainable  antecedents. 
They  contain  zymogen  granules,  easily  visible  (as  Schwalbe  first  pointed  out)  in  the 
fresh  cell,  and  prozympgen.  By  the  microchemical  reactions  for  iron  and  phosphorus 
these  elements  may  be  demonstrated  to  be  fundamentally  different  from  the  contents 
of  the  mucous  cells. 

320 


ROBERT  RUSSELL  BENSLEY  45 

As  regards  the  similarity  of  the  glands  of  Brunner  to  the  pyloric  glands  of  the 
stomach,  it  may  be  said  that  in  nearly  all  cases  examined  slight  differences  in  structure 
could  be  discerned.  I  do  not,  however,  regard  these  differences  as  of  fundamental 
importance.  Certainly  they  are  primitively  cells  of  the  same  type.  An  interesting 
fact  is  that  the  greatest  differences  between  the  cells  of  the  two  sorts  of  glands  were 
found,  in  the  series  of  animals  studied  by  the  writer,  in  those  animals  in  which  the 
stomach  was  highly  specialized.  This  fact  can  be  explained  by  the  assumption  that 
the  two  groups  of  glands  were  primitively  similar,  and  that  their  great  dissimilarity  in 
the  case  of  animals  with  specialized  stomachs  is  due  to  the  fact  that  the  pyloric  glands 
have  also  been  modified  in  the  course  of  this  specialization.  The  writer,  however, 
hesitates  to  generalize  in  this  respect  until  a  much  larger  series  of  animals  has  been 
studied  by  the  methods  employed  in  this  research. 

The  question  of  the  phylogeny  of  the  glands  of  Brunner  is  an  exceedingly  difficult 
one  to  discuss.  Up  to  the  present  the  only  clear-cut  theory  of  their  origin  advanced 
is  that  of  Oppel  (1897).  This  author  expresses  his  views  as  follows: 

Bei  zahlreichen  niederen  Wirbeltieren  finden  sich  Spuren  einer  Tendenz  der  Pylorusdriisen, 
sich  iiber  den  Sphinkter  hinaus  auszubreiten,  so  z.  B.  bei  Urodelen,  wo  eine  scharfe  Grenze 
zwischen  den  letzten  Pylorusdrusen  und  den  Darmdriisen  iiberhaupt  schwer  zu  ziehen  ist.  Die 
letzten  Pylorusdrusen  zeigen  ferner  bei  manchen  Reptilien  und  Vogeln  an  ihren  unteren  Enden 
die  Tendenz,  sich  starker  zu  entwickeln,  eine  Tendenz,  die  auch  noch  bei  SSugern  zum  Ausdruck 
kommt.  Verbinden  wir  beides,  so  werden  wir  leicht  den  Vorgang  der  Eiitstehung  der  Brun- 
nerschen  Driisen  so  deuten  konnen,  dass  die  Driisen  der  Pylorusdrusenzone  iiber  den  Sphinkter 
hinauswachsend  und  zu  einer  excessiven  Entwicklung  gelangend,  die  Muscularis  mucosae 
durchbrechen  und  so  zu  Brunnerschen  Driisen  werden. 

The  attractiveness  of  this  hypothesis  becomes  apparent  when  we  examine  such  a  case 
as  that  of  the  opossum,  in  which  the  glands  all  open  on  circumscribed  areas  of  the 
intestine,  covered  by  gastric  epithelium.  The  facts  in  favor  of  the  hypothesis  are 
briefly:  the  contiguity  of  the  glands  of  Brunner  to  the  pyloric  glands  in  the  less 
specialized  mammals;  and  the  great  similarity  of  the  cellular  components.  As  regards 
the  similarity  of  the  cells,  however,  it  must  be  remembered  that  the  cells  of  the  glands 
of  Brunner  resemble  just  as  strongly  the  mucous  cells  of  many  buccal,  cesophageal,  and 
trachcal  glands.  We  are  thus  reduced  to  the  fact  of  contiguity  as  an  effective  argu- 
ment for  the  phylogenetic  development  of  the  pyloric  glands  into  glands  of  Brunner. 
Furthermore,  in  accepting  this  hypothesis  we  must  assume  that  the  epithelium  of  the 
small  intestine  is  specifically  differentiated  from  that  of  the  stomach,  not  only  in  the 
adult,  but  in  the  embryo  at  the  time  the  glands  of  Brunner  are  formed;  that  is  to  say 
that  at  a  time  when  no  structural  differences  can  be  discerned  between  the  cells  of  the 
gastric  and  intestinal  epithelium  the  cells  actually  have  a  different  developmental 
potential,  those  of  the  stomach  having  lost  the  power  of  developing  into  cells  of  the 
intestinal  type  and  those  of  the  intestine  that  of  developing  into  cells  of  the  gastric 
type.  We  must  also  assume  that  there  is  a  mingling  of  this  gastric  hypoblast  and 
intestinal  hypoblast  in  the  region  of  the  formation  of  the  glands  of  Brunner,  because 

321 


46          THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNER 

ontogenetically  the  glands  of  Bmnner  do  not  develop  as  downgrowtks  of  pyloric 
glands,  but  develop  simultaneously  as  independent  elements  in  the  duodenum. 
Furthermore,  if  we  assume  this  extremely  early  specification  of  the  respective  epithelial 
elements  of  the  stomach  and  intestine,  how  are  we  to  explain  the  occurrence  of  glands 
of  Brunner  in  the  horse  at  a  point  seven  meters  from  the  pylorus,  and  the  relatively 
great  extent  of  the  glands  in  the  rabbit,  sheep,  pig,  and  man?  It  might,  of  course,  be 
urged  that  it  is  possible  that  in  the  rapid  growth  of  the  midgut,  gastric  epithelial 
elements  may  be  carried  a  considerable  distance  from  the  pylorus  and  there  serve  as 
foci  for  the  development  of  glands  of  Brunner.  A  similar  argument  might  be 
employed  to  explain  the  occurrence  of  characteristic  intestinal  epithelium  in  the 
stomach,  as  observed  by  Schaffer  (1897),  Boeckelman  (1902),  and  Hari  (1901).  Such 
arguments  are  unanswerable  because  they  do  not  admit  of  proof  or  disproof. 

It  does  not  seem  possible  to  me  to  reconcile  the  facts  of  the  distribution  of  the 
glands  of  Brunner  and  of  their  ontogenetic  development  with  Oppel's  theory  that  they 
are  developed  as  a  further  downward  growth  of  the  pyloric  glands  into  the  intestine. 
For  the  present  it  would  seem  to  be  more  probable  that  the  glands  of  Brunner  are 
caenogenetic  structures  developed  in  mammals  from  the  hypoblast  of  the  midgut.  The 
occurrence  of  serous  tubules  in  the  glands  of  Brunner  of  the  rabbit  is  evidence  of  a 
new  functional  need  in  the  intestine. 

Oppel  (1899)  has,  however,  promised  further  explanations  of  his  theory  to  adapt 
it  to  the  facts  of  distribution,  and  in  the  meantime  these  may  be  awaited  with  interest. 

In  conclusion  I  should  like  to  emphasize  the  fact  that  I  do  not  regard  the  evidence 
brought  forward  in  this  investigation  to  show  that  the  glands  of  Brunner  are  mucous 
glands  as  at  all  excluding  the  possibility  that  they  also  form  small  quantities  of 
digestive  ferments.  The  latter,  however,  if  they  are  formed,  are  not  present  in  suffi- 
cient quantities  to  appear  in  the  cells  as  definite  formed  elements  recognizable  by  the 
microscopic  or  microchemical  means  at  our  disposal. 


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ROBERT  RUSSELL  BENSLEY  49 

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EXPLANATION  OF  FIGURES 

For  the  drawings,  of  which  Figs.  1-11  and  Fig.  13  are  reproductions  the  author  is  indebted 
to  the  skill  of  Mr.  Leonard  H.  Wilder.  All  drawings  are  from  camera  lucida  outlines. 

PLATE    XIX 

FIG.  1. — Section  including  a  portion  of  the  pars  pylorica  ventriculi  and  the  upper  end  of  the 
duodenum  of  the  opossum,  showing  the  peculiar  defect  of  the  tunica  mucosa  on  which  the 

glands  of  Brunner  open.     X  40. 

PLATE  xx 

FIG.  2. —  Transverse  section  of  two  tubules  of  the  glands  of  Brunner  of  the  opossum. 
Ferric  alum  hnematoxylin.  The  drawing  shows  the  structure  of  the  cells  composing  these 
tubules  in  the  condition  of  incomplete  loading.  The  secretion  is  subdivided  into  a  proximal 
and  distal  mass  by  a  band  of  cytoplasm.  Some  basal  cytoplasm  still  remains  at  the  attached 
end  of  the  cell  and  around  the  nucleus.  X  1100. 

FIG.  3. — Transverse  section  of  a  tubule  of  the  glands  of  Brunner  of  the  opossum  in  the 
same  physiological  condition  as  those  in  Fig.  2,  stained  with  stronger  muchsematein.  The 
granular  character  of  the  secretion,  its  subdivision  into  two  masses,  and  the  clustering  of  the 
granules  of  the  proximal  mass  around  the  oval  or  flattened  nucleus  are  well  shown.  X  1100. 

FIG.  4. —  Tubule  of  the  gland  of  Brunner  of  the  opossum  in  the  condition  of  maximum 
loading;  iron  hsematoxylin.  The  two  masses  of  secretion  are  not  to  be  recognized,  the  trans- 
verse band  of  cytoplasm  separating  them  having  disappeared;  basal  cytoplasm  less  than  in 
Fig.  2;  nucleus  more  flattened.  X  1100. 

PLATE  xxi 

FIG.  5. — Portion  of  a  lobule  of  Brunner's  glands  of  the  rabbit,  stained  in  iron  haema- 
toxylin.  The  figure  shows  nine  mucous  tubules  and  one  serous  acinus  in  transverse  section. 
In  the  former  the  subdivision  of  the  secretion  into  two  masses  is  indicated  in  most  of  the  cells. 
X  500. 

FIG.  6. —  The  serous  acinus  shown  in  Fig.  5  more  highly  magnified.  In  each  cell  the 
outer  zone  filled  with  deeply  staining  prozymogen  and  the  inner  clear  zone  containing  a  few 
granules  of  zymogen  are  shown.  Most  of  the  zymogen  granules  which  are  present  in  the 
living  cell  have  been  lost  in  fixation.  X  1300. 

FIG.  7. — Fresh  serous  acinus  from  the  rabbit's  glands  of  Brunner  showing  inner  zone  filled 
with  zymogen  granules.  X  1300. 

FIG.  8. — A  tubule  of  Brunner's  glands  of  the  opossum.  The  section  has  been  treated  with 
water  and  then  stained  with  stronger  muchsematein.  The  granules  visible  in  Fig.  3  have  given 
place  to  a  deeply  stained  coarse-meshed  network.  X  1100. 

325 


50          THE  STRUCTURE  OF  THE  GLANDS  OF  BRUNNER 

PLATE  XXII 

FIG.  9. — Tubule  of  the  glands  of  Brunner  of  the  muskrat.  Composed  of  large  mucous 
cells  with  flattened  nuclei.  Transverse  band  of  cytoplasm  separating  the  contained  secretion 
into  two  masses  is  readily  visible.  X  720. 

FIG.  10. — Portions  of  three  pyloric  glands  of  the  muskrat.  Note  the  smaller  cells,  larger 
nuclei,  and  more  abundant  cytoplasm  as  compared  with  Fig.  9.  X  720. 

FIG.  11. — A  small  lobule  from  the  glands  of  Bruuuer  of  man.     X  190. 

FIG.  12. — A  portion  of  a  lobule  of  the  glands  of  Brunner  of  man  located  in  the  tunica 
mucosa.  The  duct  of  the  gland  opens  into  a  gland  of  Lieberklihn,  where  a  sudden  change 
in  character  of  the  cells  takes  place.  The  cells  of  the  duct  become  richer  in  secretion  the  farther 
they  are  from  the  point  of  entrance  into  the  intestinal  gland,  the  nuclei  at  the  same  time  becom- 
ing more  flattened.  In  many  of  the  cells  may  be  seen  the  transverse  band  of  cytoplasm 
separating  the  secretion  into  two  masses.  X  280. 

PLATE  XXIII 

FIG.  13. — Section  of  the  duodenum  of  man.  The  superficial  epithelium  and  portions  of  the 
villi  in  this  section  were  unfortunately  lost.  The  grouping  of  the  glands  of  Brunner  in  the 
tunica  mucosa  and  tela  submucosa  are  shown,  as  well  as  their  opening  into  the  glaudulae  intes- 
tinales.  X  66. 

PLATE  XXIV 

FIGS.  14,  15. —  Photomicrographs  of  section  of  the  duodenum  of  man  stained  in  stronger 
muchsematein.  These  figures  show  well  the  topography  of  the  glandular  lobules  as  well  as 
the  intensity  of  the  stain  which  their  contained  mucin  takes  in  this  solution.  X  37. 


326 


DECENNIAL   PUBLICATIONS,  X 


PLATE  XIX 


Beginning  of 
intestinal  epi- 
thelium and 
glands 


Defect  into 
which  glands 
of  Bruuuer 
open 


..  Central  duct 
of  lobule 
which  opens 
into  another 
defect  than  the 
one  above 


L.  H.  WILDER 


FIG.  1 


DECENNIAL  PUBLICATIONS,  X 


PLATE  XX 


Proximal  clear 
zone  contain- 
ing proximal 
mass  of 
secretion 
Distal  clear 
zone  contain- 
ing ili-tnl  mass 
of  secretion 


m-  K :/ 


Band  of 
cytoplasm 

separating  two 
masses  of 
secretion 


Cells  in  \\  hirh 
the  two  masses 
are  becoming 
confluent 


FIG.  2 


^       f,  >/.''.  /:-  ^^o,     «¥' 


L.  H.  WILDER 


FIG.  3 


FIG.  4 


DECENNIAL  PUBLICATIONS,  X 


PLATE  XXI 


•te 


•->•«/*!-;• 

«,,-.!,  -4:    :  ?v. 

•  *'••.-,. 


Serous  acinus 


~    *' 


&:?#&'.   •-: 

'*v*  ! 

4^      :•;•.:::;.. 
...  .••*.  :..  ;  ,    •••  s\*  • 

FIG.  5 

Proximal  zon 
of  coll  contain- 
ing deeply 
stained 
prozymogen 


TJistal  zone  of 
cell  containing 
a  few  granules 
of  zymogen 


Fio.  (5 


FIG.  7 


(iranules  of 
zymogen  fill- 
ing the  distal 
zone  of  the 
scrims  cell 


L.  H    WILDER 


Fio.  S 


DECENNIAL  PUBLICATIONS,  X 


PLATE  XXII 


BrunncrV 
gland  of  Fiber 


Fio.  9 


(iranular  cell 
(jf  Hamburger 

iSliilirV) 


Pyloric  glands 
of  Fiber 


Paneth  cell 


gpR^;^ 

•      ,      •        It     C''.    I 

•     \   -->w  \.  /;  ^ 
'--  f-          •       •,-'•'      .; 


Lamina 

innscularis 

mucosffi 


L    H.  WILDER 


Fio.  11 


FIG.  12 


-.1.  t       . 


DECENNIAL  PUBLICATIONS,  X 


PLATE  XXIII 


yt  MP#  ^-r'-^if^^-:-" 


Opening  of  gland  of 
Brunner  into  gland  of 
LieberkUlm 


Group  of  Brunner's 
glands  in  tunica 
mucosa 


Lamina  muscular! 


Group  of  glands  in 
tela  submucosa 


Portion  of  tela  submu- 
cosa  free  from  glands 


Part  of  circular 
muscular  coat 


L    H.  WILDER 


FIG.  13 


DECENNIAL  PUBLICATIONS,  X 


PLATE  XXIV 


.Groups  of 
glands  in  the 
tunica  mucosa, 

opening  into 
crypts  of 
Lieberkuhn 

Submucous 

group  of 
glands 


FIG.  14 


Dilated  duct 

between 
lobules 


_LobuIe  show- 
ing central 
duct  with 

radial 
branches 


R.  R.  BENSLEY 


FIG.  15 


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